Niveen Khashab, KAUST
Jean-Olivier Durand, Université Montpellier
Jeffrey Zink, Univ of California-Los Angeles
BM2.1: Magnetic-Based Systems
C. Jeffrey Brinker
Monday PM, November 28, 2016
Hynes, Level 1, Room 103
9:00 AM - *BM2.1.01
Multifunctional Nanoparticles for Photodynamic Therapy of Brain Tumors
Muriel Barberi-Heyob 1 , Thierry Bastogne 1 , Sophie Pinel 1 , Paul Retif 1 , Regis Vanderesse 2 , Olivier Tillement 3 , Francois Lux 3 , Celine Frochot 4
1 CRAN, CNRS Université de Lorraine Vandœuvre-lès-Nancy France, 2 LCPM, CNRS Université de Lorraine Vandœuvre-lès-Nancy France, 3 ILM, CNRS Université Claude Bernard Lyon Villeurbanne France, 4 LRGP, CNRS Université de Lorraine Vandœuvre-lès-Nancy FranceShow Abstract
After a brief summary of the nanoparticles developed in the field of photodynamic therapy (PDT), the presentation will focus on the interest of using of multifunctional nanoparticles for the treatment of malignant gliomas [1-2]. PDT for brain tumors appears to be complementary to conventional treatments . Number studies show the major role of the vascular effect in the tumor eradication by PDT . For interstitial PDT of brain tumors guided by real-time imaging, multifunctional nanoparticles consisting of a surface-localized tumor vasculature targeting neuropilin-1 (NRP-1) peptide and encapsulated photosensitizer and MRI contrast agents, have been designed by our group. Nanoplatforms confer photosensitivity to cells and demonstrate a molecular affinity to NRP-1 . Intravenous injection into rats bearing intracranial glioma exhibited a dynamic contrast-enhanced MRI for angiogenic endothelial cells lining the neovessels mainly located in the peripheral tumor. By using MRI completed by NRP-1 protein expression of the tumor and brain adjacent to tumor tissues, we checked the selectivity of the nanoparticles [5-6]. This is the first in vivo proof of concept of closed-head iPDT guided by real-time MRI using targeted ultrasmall nanoplatforms. Another approach will be also discussed: the combination of radiotherapy and PDT for the treatment of malignant cerebral gliomas [1-3], employing scintillating nanoparticles. With this novel therapeutic approach limited light penetration problem could be overcome and activation of the photosensitizer within tumors is performed using ionizing radiation [7-9].
1.Bechet et al., Trends Biotechnol., 26, 612-21, 2008.
2.Bechet et al., Cancer Treat. Rev., 40, 229-41, 2014.
3.Benachour et al., PLOSOne, 7,e48617, 2012.
4.Mriouah et al., Trends Biotechnol., PMID: 23021636, 2012.
5.Benachour et al., Theranostics, 2, 889-04, 2012.
6.Bechet et al., Nanomedicine NBM, 2014.
7.Bulin et al., J. Phys. Chem., 117, 21583-89, 2013.
8. Retif et al., Theranostics, 5(9):1030-1044, 2015.
9. Retif et al., Int. J. Nanomed, in press, 2016.
9:30 AM - BM2.1.02
Surface Charge, Concentration and Kinetics of Magnetic Nanostructures Uptake by Foam Cells
Luong Nguyen 1 , Krishna Radhakrishnan 1 , Vikas Nandwana 2 , Colby Thaxton 2 , Vinayak Dravid 2 , Subbu Venkatraman 1 , Kee Woei Ng 1
1 Nanyang Technological University Singapore Singapore, 2 Northwestern University Evanston United StatesShow Abstract
Atherosclerosis is a disease in which lipid containing plaques are built up on the inner walls of large and medium-sized arteries. This silent progress usually occurs for decades until the manifestation of severe clinical events such as myocardial infarction, myocardial ischemia and stroke. Therefore, it is critical to develop non-invasive, reliable and reproducible imaging techniques to diagnose atherosclerosis before the occurrence of the clinical events. Magnetic nanostructures (MNS) are promising contrast materials for high-resolution magnetic resonance imaging (MRI) to monitor plaque progression and regression. In this study, monodisperse MNS with Fe3O4 nanoparticles as core were synthesized and then functionalized with polyethylene glycol (PEG) by using NDOPA-PEG(600)-COOH. The resultant MNS-PEG had a pristine size of ~ 8 nm (by transmission electron microscopy – TEM) and a hydrodynamic size of ~ 91 nm (by dynamic light scattering – DLS). Human foam cells – lipid laden macrophages found in atherosclerosis plaques – were produced from THP-1 monocytes to investigate the toxicity and uptake of the nanoparticles. Our cell metabolism study showed that MNS-PEG concentrations up to 10 μg/mL were not toxic to foam cells while uptake was significantly dependant on time and concentration. The minimum MNS-PEG administered concentrations to result in positive Prussian blue staining in the foam cells were 50 and 5 μg/mL, respectively, for 2 and 24 hr exposure. We further examined the effects of surface charge on cellular uptake by coating MNS-PEG with different biopolymers, heparin (HEP) and protamine (PRM), using a layer by layer assembly technique. The zeta potentials of MNS-PEG, MNS-PEG-HEP and MNS-PEG-PRM were -43, -21 and +20 mV, respectively. Our results showed that foam cells only preferred to uptake negatively charged particles. Compared to foam cells, macrophages had double the capacity to uptake the MNS-PEG, while THP-1 monocytes did not show any uptake of these particles. As such, the amount of MNS-PEG uptaken by foam cells can be controlled by its surface charge, concentration and incubation time. Surface charge modified MNS have the potential to be further developed as a contrast agent for early detection of atherosclerotic plaques.
9:45 AM - BM2.1.03
Magnetically Triggered Release through Stealth Liposomes Incorporated with Iron Oxide Nanoparticles
Mudassar Virk 1 , Behzad Shaghasemi 1 , Erik Reimhult 1
1 Biological Inspired Materials, Nanobiotechnology University of Natural Resources and Health Sciences Vienna AustriaShow Abstract
Stealth (PEGylated) liposomes have taken a central role in drug formulation and delivery combining efficient transport with low nonspecific interactions. Controlling rapid release at a certain location and time still remains a challenge dependent on environmental factors. Liposome-nanoparticle composite vesicles can overcome the dependence on the local environment by providing the possibility to directly manipulate the vesicle structure by external fields. Here we report a new method by combining solvent inversion and sonication to efficiently assemble and load superparamagnetic iron oxide nanoparticles (SPIONs) into liposomes. The new method demonstrates efficient loading of both SPION and a water-soluble model drug into small unilamellar liposomes (D ~ 50 nm) using a protocol that allows us to generally and independently control nanoparticle fraction and lipid composition (Tm) in the entire relevant range. Furthermore, we show how passive release is suppressed by detailed control over the stealth liposome assembly. Therefore, for the first time, the influence of lipid and SPION composition as well as structure on the magnetically triggered release kinetics could be investigated and optimized. Complete external control over the release kinetics from burst to pulsed gradual release is thereby demonstrated and the hypothesized mechanism for local magneto-thermal release investigated and verified.
10:00 AM - BM2.1.04
Polycatechol Nanoparticle MRI Contrast Agents
Yuran Huang 1
1 Biochemistry and Chemistry Department, Materials Science and Engineering Program University of California, San Diego La Jolla United StatesShow Abstract
In this paper, we report the development of two kinds of polymeric micellar nanoparticles (sphere and cylinder) prepared from amphiphilic tri-block copolymers containing Fe(III)-catecholate complexes as new T1-weighted imaging agents with high relaxivity, low cytotoxicity, and long-term stability in biological fluids (serum and cell media). Relaxivity values of such nanoparticles are slightly higher than established gadolinium chelates and synthetic melanin-Fe(III) complex across a wide range of applied magnetic field strengths, which might be the result of long-lived second sphere water molecules hydrogen bonding with polar groups around metal ion centers inside the nanoparticles as suggested by 1H NMRD. More interestingly, shape-dependent in vitro MRI performances of different micellar nanoparticles in Hela celles were also observed, suggesting new opportunities to optimize new parameter in the design of those self-assembled poly(Fe(III)-catecholate) nanoparticles for biodiagnosis that can not be achieved by synthetic melanins. We describe these materials in an initial proof-of-concept study and propose that this class of polycatechol-based shaped nanoparticle will be suitable for pre-clinical investigations where gadolinium-free, safe and effective T1-weighted imaging by MRI contrast is highly desirable.
10:15 AM - BM2.1.05
Magnetic Nano-Switch for the Control of Cell Death Signaling
Mi Hyeon Cho 1 2 3 , Seulmi Kim 1 2 3 , Tae-Hyun Shin 1 2 3 , Dongwon Yoo 1 2 , Jinwoo Cheon 1 2 3
1 Institute for Basic Science Seoul Korea (the Republic of), 2 Yonsei-IBS Institute, Yonsei University Seoul Korea (the Republic of), 3 Department of Chemistry, Yonsei University Seoul Korea (the Republic of)Show Abstract
Finely regulated cell signaling is critical for controlling a number of cellular activities, such as differentiation, growth, and death. Magnetic nanoparticles have emerged as an important tool for the remote and noninvasive regulation of cell activities. In this study, we demonstrate a magnetic nano-switch, composed of magnetic nanoparticles conjugated with a targeting antibody, for activation of apoptosis signaling. Death receptor mediated extrinsic apoptosis signaling, one of the major targets for recent cancer therapy, is activated on cancer cells by magnetic nanoparticles under magnetic field. In addition, magnetic nano-switch can selectively induce cancer cell death in a single-cell level with the use of non-invasive external stimuli (e.g., magnetic field) which can give additional advantages of precision therapeutics with space and time selectivity for disease treatments with reduced off-target side effects. The efficacy of the newly developed magnetic nano-switch is comparable to that of the well-known death ligand, TRAIL. Moreover, it has demonstrated that it is possible to activate apoptosis signaling in vivo using magnetic nano-switch.
10:30 AM - BM2.1.06
Upconversion Nanocrystals as Optical Nanothermometers for Local Interior Temperature Characterization in Magnetically Heated Mesoporous Drug-Delivery Nanoparticles
Juyao Dong 2 1 , Jeffrey Zink 2
2 Department of Chemistry and Biochemistry University of California, Los Angeles Los Angeles United States, 1 Massachusetts Institute of Technology Cambridge United StatesShow Abstract
Magnetically induced heating of nanomaterials is being intensively studied for applications in hyperthermia therapy and drug delivery, yet the heating efficiency is usually characterized by macroscopic methods and little is known about the immediate nano environment temperature change. We are interested in quantifying this event on the nanoscale and comparing it with the observed macroscopic result. For this purpose, dual-core mesoporous silica nanoparticles were synthesized, where a lanthanide nanocrystal is embedded together with a magnetic nanocrystal. The magnetic nanocrystals generate heat in a high frequency oscillating magnetic field and the upconversion emission of the lanthanide nanocrystals shows a ratiometric response to the temperature variation as a result of two thermally coupled excited states. Thus, the silica nanoparticle interior temperature increase upon placing it in an oscillating magnetic field is quantified by the luminescence emission spectra. We found that the nanomaterial heating efficiency is related to the exposure time and the field strength of the magnetic field as well as the magnetic nanocrystal size. More importantly, the silica nanoparticles experience a much greater temperature increase than the surrounding media during the heating process. Our method measures local temperatures on the nanoscale and provides the information necessary to monitor and control the temperature for biomedical applications.
10:45 AM - BM2.1.07
Magneto-Mechanical Stress Effects on Cell Growth via Magnetic Field Dancing Modes of Magnetic Nanoparticles
Katerina Spiridopoulou 2 , Nicoletta Karypidou 1 , Nikos Maniotis 1 , Antonis Makridis 1 , Eirini Myrovali 1 , Theodoros Samaras 1 , Mavroeidis Angelakeris 1 , Katerina Chlichlia 2 , Orestis Kalogirou 1
2 Department of Molecular Biology and Genetics Democritus University of Thrace Alexandroupolis Greece, 1 Department of Physics Aristotle University of Thessaloniki Thessaloniki GreeceShow Abstract
Novel applications of magnetic nanoparticles (MNPs) demonstrate their promise towards revolutionizing the field of biomedical research in various ways. MNPs,being a versatile imaging, detecting, targeting and therapeutic platform, enable new interdisciplinary approaches in experimental design in basic and translational research such asthe development and application of multimodal therapystrategies against cancer. We examined the effect of magneto-mechanical stress induced by endocytosed single-domain magnetic nanoparticles in an applied low frequency alternating magnetic field (AMF), on the proliferation rate of the human colon cancer cell line HT29. We used commercial ferrofluids (Chemicell GmbH) consisting of an aqueous dispersion of biocompatible starch-covered magnetic particles with a magnetite core, with an average hydrodynamic diameter of 100 and 200 nm. For the application of the magnetic fields, a fundamentally different from prior setups 3D printout of a polymer rotating holder was manufactured, with a DC rotating motor operating with variable voltage (3-12V) resulting in tunable rotation frequency and capable of generating magnetic fields of variousconfigurations and parameters (f=0-20 Hz, Βo=0-200 mT). Seven characteristic three dimensional permanent magnet systems (AC, DC and rotating low frequency fields), whose component parts were NdFeB block magnets of several sizes and shapes, homogeneously magnetized in arbitrary direction, were employed. All magnet configurations used, were simulated, and the magnetic flux density was computationally calculated with COMSOL Multiphysics. Our findings suggest that the applied field frequency affects cell growth 72 hours post treatment. Interestingly, AC configurations induced cell growth, with a tendency to enhance cell proliferation by applying higher field frequencies, not only in MNPs-treated cells, but also in control, untreated cells exposed to the same field. Inhibition of cell proliferation was observed at the highest magnetic flux density values at all cases. The proposed novel setup represents a versatile and accurate systemfor studying,biological effects of magneto-mechanical stress in vitro.
11:30 AM - BM2.1.08
Nanomagnetic Force Probe for Investigation of the Audio Frequency Tonotopy of Hair Cell
Ji-wook Kim 1 2 3 , Eunna Chung 1 2 3 , Hongsuh Choi 1 2 3 , Jung-Uk Lee 1 2 3 , Daehyun Kim 1 2 3 , Jinwoo Cheon 1 2 3
1 Institute for Basic Science Seoul Korea (the Republic of), 2 Yonsei-IBS Institute, Yonsei University Seoul Korea (the Republic of), 3 Department of Chemistry, Yonsei University Seoul Korea (the Republic of)Show Abstract
Sound perception via mechano-sensation is a remarkably sensitive and fast transmission process, converting sound as a mechanical input to neural signals in a living organism. Although knowledge of auditory hair cell functions has advanced over the past decades, challenges remain in understanding their biomechanics, partly because of their biophysical complexity and the lack of appropriate probing tools. In this study, we present nanomagnetic force probes (nano-MFP) as a non-contact and ultrafast mechanical actuator to explore the audio frequency tonotopy of avian hair cells. The nano-MFP is designed to remotely deliver full avian audible frequency stimuli (50 ~ 5,000 Hz) to individual hair cell with spatial specificity in the tonotopic axis of the cochlea. The working principle of the nano-MFP is the use of a magnetic force generated from an electromagnetic probe tip, which is a non-contact stimulation enabling measurement of truly free-standing hair bundle motility. The switching rate of the magnetic field can be accurately controlled down to 9 μs, which corresponds to approximately 50 kHz, covering full-range audio frequency of avian, mammalian, and rodents. The hair bundle biomechanics in the full range of the avian cochlea which has different oscillatory dynamics were probed by using a nano-MFP. Two time constants are measured from the recovery motion of the avian hair bundle: one is related passively to the morphology of hair bundle, and the other is active and changing according to the applied stimulus and media condition, which shows the avian hair bundle possess biologically active components. Stimulating the full-range audio frequency of the individual hair bundles on the avian cochlea reveals that there exists tonotopic frequency specificity in hair bundles. The precise spatiotemporal controllability of our nano-MFP reported gives great promise to explore important questions in a variety of biomechanics research that have been difficult to answer with conventional probing techniques.
11:45 AM - BM2.1.09
Magnetic Particle Assisted Highly Sensitive DNA Detection Using Quantum Dot-Fullerene-Based Molecular Beacons
Ye Liu 1 , Li-Jing Cheng 1 , Akash Kannegulla 1
1 Oregon State University Corvallis United StatesShow Abstract
We present a high-sensitive DNA detection method using quantum dot (QD)-fullerene (C60) based molecular beacons (MBs) assisted by magnetic nanoparticles. In this molecular beacon configuration, C60 serves as an efficient quencher and CdSe/ZnS core-shell QD, the fluorophore. When C60 and QD are located nanometer away from each other, C60 efficiently uptakes photo-induced electron transferred from the QD and quenches QD emission. We observed about 60% of quenching efficiency in covalently incorporated QD-C60 complex with 1:1 QD-to-C60 ratio. Note that the quenching efficiency could be higher as the commercial QD employed in this experiment contains a 4-nm thick polymer coating which retards the electron transfer between QD and C60. The inorganic QD-C60 MB is developed to overcome the low signal-to-noise ratio and photobleaching issues in traditional organic dye based MBs. The MB probes were further attached on 200-nm sized magnetic particle to form a QD-C60 MBs@MNP complex that facilitates manipulation of the probes in analytes using external magnetic field.
The DNA detection assay started with adding 5 ul QD-C60 MBs@MNP solution in 5 ul analyte samples of various target DNA concentrations ranging from 10 fM to 1 uM. Hybridization takes 20 minutes. The solution was then loaded to a 500 um-thick flow cell for fluorescence analysis covered with silver coated reflector. The fluorescence imaging of hybridized molecular beacons was captured using monochromatic CMOS camera followed by measuring the photo-count of each sample. The QD-C60 MB provides highly sensitive detection with strong signal-to-noise ratio. No photo bleaching effect was observed. The detection limit of < 100 pM was observed. DNA detection based on QD-C60 MBs@MNP is featured by its high sensitivity, stability, and low-volume assay. By applying external magnetic field to concentrate MBs, it is possible to amplify the fluorescence signal and therefore further reduce the detection limit. The sensitive detection method will find applications in the analysis of low-concentration target nucleic acids, such as cancer related circulating miRNA. In addition, the QD-based sensing configuration can be extended for multi-target detection by coding multiple MB probe sequences with different QD emission colors.
12:00 PM - BM2.1.10
Biosynthesized Magnetite Nanoparticles—From Adhesion to MRI for Specific Targeting of Triple Negative Breast Cancer
John Obayemi 1 , Jingjie Hu 1 , Vanessa Uzonwanne 1 , Karen Malatesta 1 , Nicolas Anuku 1 , Winston Soboyejo 1
1 Mechanical and Aerospace Engineering Princeton University Princeton United StatesShow Abstract
In the search for specific targeting of breast cancer cells, one of the mechanism in the use of functionalized nanoparticles is driven by nanoparticles-cells interactions. Significant studies done on nanoparticles-cell adhesion are yet to give insights at a nanoscale of ligands/antibody conjugated magnetite nanoparticles adhesion to cancer/normal breast cells. This paper presents the results of an experimental study of the adhesion forces between components of model conjugated magnetite nanoparticle systems/configurations for improved selectivity in the specific targeting of breast cancer. In this study, Atomic Force Microscope (AFM) was use to unravel and measure the adhesion interaction between biosynthesized magnetite nanoparticles (BMNPs)/conjugated BMNPs and breast cancer (MDA-MB-231) cells/normal breast (MCF 10A) cells. In each case, chemically synthesized magnetite nanoparticles (CMNPs) and conjugated CMNPs were used as a control. The BMNP constituents had adhesion forces (to breast cancer cells and normal breast cells) that were greater than that of CMNPs. The increased in adhesion interactions of BMNPs systems are attributed to Van der Waals interactions between conjugated nanoparticles and the over-expressed receptors (revealed by confocal images via immunofluorescence staining) on the surfaces of the breast cancer. In vivo studies also showed evidences of improve selectivity and specificity of conjugated BMNPs in detection of triple negative breast cancer via MRI imaging. The implication of the results suggest the potential use of BMNPs conjugates for rapid screening of potentials ligands/antibodies as well as the design of robust conjugated BMNPs as a contrast agent for enhancing magnetic resonance imaging (MRI) for specific targeting of triple negative breast cancer.
12:15 PM - BM2.1.11
Cellular Engineering for the Remote-Controlled Delivery of Therapeutics
Shreyas Shah 1
1 Physiological Communications Nokia Bell Labs New Providence United StatesShow Abstract
Stem cells have a number of useful properties, including their ability to proliferate, migrate and differentiate. For this reason, numerous clinical studies have utilized stem cell-based therapies for the treatment of various human diseases and disorders. An emerging area of interest lies in engineering cells to further enhance their innate abilities and confer them with new functionalities. Cellular-based gene therapies is one such example, wherein stem cells are genetically engineered to express therapeutic molecules. Such approaches have shown tremendous potential for cancer applications since stem cells have an innate ability to home to tumors. However, traditional stem cell-based gene therapies are hampered by the inability to control when the therapeutic genes are actually turned on, thereby resulting in detrimental side effects.
Herein, we report the novel application of magnetic core-shell nanoparticles for the dual purpose of delivering and activating a heat-inducible gene vector that encodes TNF-related apoptosis-inducing ligand (TRAIL) in mesenchymal stem cells (MSCs). By combining the tumor tropism of the MSCs with the spatiotemporal magnetic nanoparticle-based delivery and activation of TRAIL expression, this platform provides an attractive means with which to enhance our control over the activation of stem cell-based gene therapies. In particular, we found that these engineered cells retained their innate ability to proliferate, differentiate, and, most importantly, home to tumors, making them ideal cellular carriers. Moreover, exposure of the engineered cells to mild hyperthermia, by applying an alternating magnetic field, resulted in the selective expression of TRAIL from the engineered cells. As a result, significant cancer cell death was induced both in vitro and in vivo. Overall, stimuli-responsive stem cell-based gene therapy using multifunctional nanoparticles has immense potential for both cancer and other biomedical applications.
12:30 PM - *BM2.1.12
Magnetically Responsive Nanocarriers for Imaging-Guided Delivery
Zhihong Nie 1 , Kuikun Yang 1 , Yijing Liu 1
1 University of Maryland College Park United StatesShow Abstract
Inorganic nanoparticles (NPs) have been widely explored for the treatment, diagnosis, and detection of many diseases, because of their unique features as compared with their organic and polymeric counterparts. Among others, the response of superparamagnetic NPs such as iron oxide NPs (IONPs) to magnetic fields enables their contrast-enhanced magnetic resonance imaging (MRI), effective hypothermia therapy, and targeted delivery of therapeutic agents. The assembly of IONPs with polymers enhances their stability and biocompatibility in physiological environment, as the hydrophobic nature of these NPs synthesized by solvothermal synthesis approaches makes them unsuitable for direct use in biological conditions. Moreover, the clustering of MNPs within such as vesicular membranes can dramatically increase the MRI contrast and responsiveness to external magnetic field, because of their size-dependent transverse relaxivity and magnetic moment. In particular, vesicles embedded with IONPs in the membrane are ideal candidates of delivery vehicles, thanks to their high drug loading content, magnetically-triggered release, and high magnetization per vesicle. To date, a variety of IONPs-bearing vesicles (e.g., liposomes or polymersomes) have been developed for hyperthermia therapy and targeted chemotherapy. However, most of existing platforms suffer from insufficient magnetization or limited capability of encapsulating hydrophilic or hydrophobic drugs. To tackle the challenge, we have recently developed a versatile strategy for the design of drug-encapsulated magnetic nanovesicles with extremely high loading of IONPs (and gold NPs) in the polymer membrane for imaging-guided targeted delivery of therapeutics. In this talk, I will present the self-assembly of polymer-functionalized IONPs (and gold NPs) into vesicles with densely packed IONPs in the membrane and the application of the nanocarriers for imaging-guided chemotherapy of tumors and localized drug delivery for uveitis treatment.
BM2.2: Si and Ti-Based Systems I
Monday PM, November 28, 2016
Hynes, Level 1, Room 103
2:30 PM - *BM2.2.01
Mesoporous Silica Nanoparticle Supported Lipid Bilayers (Protocells) for Individual Cell Targeting and CRISPR Delivery
Paul Durfee 2 , Ayse Muniz 3 , Yu-Shen Lin 2 , Kim Butler 2 , C. Jeffrey Brinker 1 2
2 Chemical and Biological Engineering University of New Mexico Albuquerque United States, 3 Biochemistry University of New Mexico Albuquerque United States, 1 Sandia National Laboratories Albuquerque United StatesShow Abstract
Mesoporous silica nanoparticle-supported lipid bilayers (protocells) are an emerging class of nanocarriers that synergistically combine the advantages of mesoporous silica nanoparticles (MSNs), including tunable size, shape, and pore characteristics that facilitate high loading capacities, with the advantages of liposomes such as enhanced circulation, ease of synthesis, biocompatibility, flexible formulations, and capacity for targeting. Protocell assembly occurs upon fusion of the liposome to the surface of the MSN, resulting in encapsulation of the MSN core within a conformal supported lipid bilayer (SLB). Further conjugation of the SLB with polymers, such as PEG, or targeting ligands confer stability and enable specific binding and internalization. We have demonstrated this platform to be a plug-and-play nanocarrier, capable of housing disparate cargos ranging from small molecule drugs for cancer therapeutics to large biomolecules including large DNA constructs such as plasmids for use in gene therapy and applying recently developed CRISPR-Cas9 technology for precise gene editing and modulation. Furthermore, the flexibility of the system extends to the targeting potential viz surface chemistries that accommodate antibodies, affibodies, and other molecules to enhance cell-specific delivery. Zwitterionic protocells conjugated with an anti-EGFR antibody and loaded with the cytotoxic drug gemcitabine preferentially bound to and killed individual EGFR-positive REH leukemia cells ex ovo and avoided their EGFR-negative counterparts while maintaining properties that are generally viewed as necessary for successful therapeutic efficacy. These properties include size monodispersity, high colloidal stability over time, minimal nonspecific binding or uptake by the mononuclear phagocytic system, high capacity for and precise release of therapeutic cargos, and low cytotoxicity. Furthermore, cationic protocell formulations can package and deliver large plasmid constructs that encode for CRISPR-Cas9 components. In a HER-2 expressing cell line, protocells modified with an anti-HER-2 affibody successfully targeted and delivered plasmids resulting in GFP and RFP expression, demonstrating successful CRISPR delivery. Unmodified protocells were used for transfection of Cas9-mediated activation of TP53, resulting in increased p53 production. Overall we have demonstrated the potential of the protocell as a platform nanocarrier capable of targeting a range of cell-surface markers and delivering diverse cargos while maintaining advantageous properties that will be necessary for viable in vivo use.
3:00 PM - *BM2.2.02
Multifunctional Mesoporous Nanoparticles Interacting with Cells
Thomas Bein 1
1 University of Munich Munich GermanyShow Abstract
The integration of multiple molecular functionalities into mesoporous silica nanoparticles (MSNs) enables the development of nanoagents for targeted drug delivery, as well as diverse imaging agents. We will provide an overview on our research regarding the synthesis of mesoporous nanoparticles, approaches towards targeting certain cell receptors, as well as controlled molecular release systems based on internal (such as pH and redox potential) and external (light, temperature, etc.) stimuli.
Folate and epidermal growth factor (EGF) has been used for successful cell targeting with MSNs. Considering triggered release in the endosome, a novel pH-responsive system has been created based on genetically modified carbonic anhydrase (CA) gatekeepers. This system relies on the spatial control of functionalization available for our previously developed mesoporous silica core-shell nanoparticles. A pH-dependent CA inhibitor was covalently attached to the surface of the MSN, resulting in the desired opening mechanism caused by the endosomal pH change.
Addressing endosomal escape, we have covalently attached a red-light sensitive phthalocyanine photosensitizer to the MSN, surrounded by a lipid bilayer. Photoactivation leads to endosomal membrane rupture in cells causing cargo release from the mesopores into the cytosol. Moreover, we have exploited the proton sponge effect during acidification of the endosome with polymer-functionalized MSN to achieve endosomal release. Selective extracellular release of bioactive molecules has also been achieved, taking advantage of overexpressed matrix metalloproteinases in cancer tissue. These enzymes were used to open an MSN release mechanism with high spatial selectivity.
It is of great interest to expand the scope of bioactive cargo molecules that can be released from MSN systems. We have developed organically functionalized large-pore and medium-sized pore MSNs with spatially controlled orthogonal functionalities that can reversibly adsorb oligonucleotides such as siRNA. Very high siRNA loading in the internal pore volume, efficient endosomal release and high biological activity was established. Moreover, cellular uptake of proteins such as small antibody fragments was successfully achieved using a novel release mechanism from MSNs. These antibodies were used to label cellular organelles with high specificity.
These and other examples demonstrate that mesoporous silica nanoparticles represent a promising and highly flexible platform for numerous biomedical applications.
3:30 PM - BM2.2.03
PEI-PEG Copolymer Gated Dendritic Mesoporous Silica Nanoshuttles for Targeting Cancer—Encapsulation of TNF-α
Arne Kienzle 1 , Sven Kurch 1 , Janine Schloeder 1 , Nikolas Haass 2 , Wolfgang Tremel 1 , Helmut Jonuleit 1
1 University of Mainz Mainz Germany, 2 Translational Research Institute University of Queensland Brisbane AustraliaShow Abstract
A main challenge in nano-biomedicine is the engineering of nanostructures or nanomaterials that can efficiently encapsulate drugs at high load, cross cell membranes, and controllably release their cargo at target sites. One strategy to bypass the generic toxicity associated with the drug as often seen in cancer therapy is to entrap drugs into engineered mesoporous silica nanoparticles. Their pore sizes are tunable to fit different cargo sizes. Their framework is stable, their surface can be modified with different functionalities which permits a passive or active targeting of the tumor site. This enables an efficient drug payload into the malignant cell of tumors, while the non-malignant cells become minimally impacted.
TNF-α is one of the well-known anti-tumor factors. Due to its cytotoxic effect on tumor cells and its pro-inflammatory potential, TNF-α has the ability to slow down tumor growth. However, its pharmacological use is dramatically limited by its high systemic toxicity. Therefore, we devised a drug delivery system combining TNF-α loaded, dye functionalized dendritic mesoporous silica nanoparticles with a pH-sensitive PEI-PEG copolymer for pore coverage. The major objective of this study was the transport of TNF-α in a nontoxic carrier system followed by a tumor tissue specific release to induce anti-tumor activity without causing systemic toxicity.
We demonstrate the combination of mesoporous silica nanoparticles for transport and pH-sensitive PEI-PEG copolymer for pore coverage as a potent system allowing the transport of toxic anti-tumor biologicals. MTT assays were used to analyze the biological activity of encapsulated TNF-α. Solubility and functionalization of the mesoporous silica nanoparticles were monitored by zeta potential, dynamic light scattering and transmission electron microscopy measurements. Following the functionalization with anti-EGFR-antibody, which was controlled by FACS, mesoporous silica nanoparticles are tailored for use in humanized, tumor-bearing NOD/ScidtgHLA-A2+ mice.
Encapsulated TNF-α showed a 97% reduced toxicity compared to free TNF-α after 12h of treatment. TEM, DLS and zeta potential demonstrated stable and functional particles under normal culture conditions. FACS data demonstrated successful anti-EGFR conjugation to the particles PEI-PEG copolymer. Particle distribution in 3D tumor spheroids was studied by transducing C8161 cells with FUCCI (fluorescence ubiquitination cell cycle indicator) and growing as 3D tumor spheroids. Within 24h of treatment the silica particles were found throughout the spheroids. Whereas silica nanoparticles did not appear influence the cell cycle, TNF-α loaded particles induced G1 arrest before causing cell death. Our results allow further investigation using anti-EGFR functionalized DMSN to limit systemic toxic TNF-α effects in vivo.
4:15 PM - *BM2.2.04
Stimulus Responsive Nanomaterials
Luisa De Cola 1
1 University de Strasbourg Strasbourg Cedex FranceShow Abstract
Porous materials and capsules are interesting nano/micro system able to entrap desired molecules and act as delivery or imaging species. They can be created using soft species such as gels or polymers or inorganic precursor to obtain microporous and mesoporous silica based nanoparticles. In this talk I will focus on silica-based materials, and discuss how we can overcome the problem related to the fate of inorganic nanocontainers in in vitro and in vivo applications. Indeed the issue related to the use of materials for therapy and imaging in living organism, is their accumulation in vital organs that often prevent their use.
Recently, a new generation of breakable hybrid nanoparticles (NPs), able to response and degrade upon external stimuli (e.g. reductive agents, pH, etc.), have been developed in our group1,2. The insertion of responsive linkers in the framework of these particles, results not only in the destruction and safe excretion of the nanoparticles from the cells, but also in a faster and better delivery of the payloads (see scheme 1). Moreover, to expand the breakability properties of this material for other purpose, the possibility to entrap proteins into a breakable silica shell has also been realized in our laboratory3. It has been shown that the activity of different proteins (Cytochrome C, EGFP, TRAIL Apo2 and onconase) remains intact after their delivery into cancer cells.
1. Maggini.L et al, Nanoscale, 2016 , 7240-7247
2. Maggini.L et al, Chem. Eu. J., 2016, 22, 3697-3703
3. Prasetyanto, E.A. et al, Angew. Chem. Int. Ed. 2016, 3323–3327
4:45 PM - *BM2.2.05
Nanoparticles for Cancer Theranostic
Magali Gary-Bobo 1
1 Institut des Biomolécules Max Mousseron Centre National de la Recherche Scientifique Montpellier Cedex 5 FranceShow Abstract
Currently, cancer screening campaigns are widespread and allow early lesion detection. These small tumors with weak aggressive potential in the short term do not justify heavy treatment such as surgery or chemotherapy, and prompt the consideration of minimally invasive treatments. Recently, the development of nanosciences in the fight against cancer has been the object of tremendous efforts. In this context, the development of biodegradable and biocompatible nanotools could be of particular interest to achieve the combination of targeting, imaging, drug delivery and photodynamic therapy of cancers. Based on our recent results obtained through multidisciplinary and international collaborations we tried to develop a breakthrough technology in the field of nanomedicine. Membrane receptors overexpressed by cancer cells were identified and mesoporous silica nanoparticles carrying active molecules for imaging and therapy were developed and grafted with ligands specific of these receptors. This work at the interface between fundamental and applied research could lead to the design of effective and biocompatible prototypes for personalized medicine.
5:15 PM - BM2.2.06
Controlled Cargo Release from Mesoporous Silica Nanoparticles through Localized Heating
Bastian Ruehle 1 , Jeffrey Zink 1
1 University of California, Los Angeles Los Angeles United StatesShow Abstract
Mesoporous silica nanoparticles (MSNs) have attracted much attention in recent years due to their growing impact on various fields such as catalysis, storage and separation, and biomedical applications including bioimaging and biosensing, diagnostics and theranostics, bone and tissue engineering, and drug delivery. Their well-defined periodic pore system and their enormous flexibility regarding functionalization enable them to accommodate a variety of different guests. Moreover, using specific functionalization and design allows for controlled and targeted drug delivery from silica nanocarriers to specific target sites, such as cancer cells. However, there is still a great demand for spatial and temporal control of the release via external, non-invasive methods of actuation.
A particularly interesting concept of external actuation is the localized generation of heat at the intended target site that can trigger cargo release from suitably capped mesoporous silica nanoparticles. Examples of such a localized heating include high intensity focused ultrasound (HIFU) or superparamagnetic heating of iron oxide core – mesoporous silica shell nanoparticles in alternating magnetic fields (AMF). HIFU causes local heating due to focused sound waves, and superparamagnetic heating in AMFs causes a local increase in temperature of the nanoparticles that can be much higher than that in the bulk solution. Both modes of actuation feature good tissue penetration and are non-invasive and biocompatible. In this contribution, we will discuss how we can use these concepts of localized heating to design mesoporous silica nanoparticles that release their payload upon external actuation, thus giving spatio-temporal control over the triggered release process.
BM2.3: Poster Session I
Tuesday AM, November 29, 2016
Hynes, Level 1, Hall B
9:00 PM - BM2.3.01
Design of Zeolite Modified Electrodes and Their Influence on Biosensor Performance
Burcu Akata Kurc 1 , Berna Ozansoy 1
1 Middle East Technical University Ankara TurkeyShow Abstract
Enzyme-based biosensors have been of intense investigation and field-effect transistor (FET)-based sensors are one of the widely produced, miniaturized silicon-based semiconductor devices used to quantify ion concentrations in the analyte solution. Overall, current research has focused on enhancement of the sensitivity, detection limit, selectivity and the storage stability of these electrochemical biosensors. For this purpose, variety of modification methods on electrochemical biosensor surfaces is proposed. At present, use of new nanosized materials in biosensor design is a promising approach to improve analytical characteristics of the devices. Zeolites are perspective nanomaterials for biosensor modification. They are inorganic compounds, the structure of which is a crystal lattice consisting of alumina and silica tetrahedra bound by oxygen atoms. This framework forms a lot of pores and channels which considerably increases the zeolite surface. In the current study, a review on precise control over structural and chemical properties of zeolites and their consequent effect on electro-chemical biosensors will be given. All results suggest that the methodology of surface immobilization and zeolitic properties such as Si/Al ratio, surface roughness, particle size, hydrophilicity and the ability to create gold nanoparticles within the nanopores effect and ultimately enhance the biosensor sensitivity and stability. Considering the important biological role of urea as a diagnostic indicator of kidney failure and major uremic toxin, its determination was needed in medical diagnostics. It was shown that distinction of healthy people from people with renal dysfunction became easier by zeolite modified biosensors. Our results show that the performance of constructed ISFET-type biosensors strongly depends on Si/Al ratio of employed zeolite nanoparticles as well as the type of enzymatic reaction employed. All fabricated biosensors demonstrated high signal reproducibility and stability. The obtained results were used for the development and design for an experimental prototype of novel nanobiosensor located implant.
9:00 PM - BM2.3.02
Bacteria-Responsive Mesoporous Silica Nanoparticles Gated with Lysozyme-Gold Cluster Coatings for Monitoring Surfaces Bacterial Contamination
Shahad Alsaiari 1 , Mohamed Amen Hammami 1 , Niveen Khashab 2
1 King Abdullah University of Science and Technology Thuwal Saudi Arabia, 2 King Abdullah University of Science and Technology Kaust Saudi ArabiaShow Abstract
Effective detection and sensing of surfaces bacterial contamination is demonstrated. We have designed a multifunctional mesoporous silica-gated AuNCs@lys nanocarrier for sensing and killing bacteria. Our system offers a selective damage and sense of the bacterial walls; through the synergistic effect of lysozyme and kanamycin. The fluorescence of AuNCs decreases upon their interaction with bacterial cell wall, which allows us to monitor bacteria-nanoparticle interaction. The enhanced stability of AuNCs@lys (negatively charged) is obtained by immobilizing it on the positively charged silica via electrostatic interactions. The as prepared nanoparticles are embedded on Poly(ethylene oxide)/poly(butylene terephthalate) copolyether ester, (PEO/PBT copolymers) to fabricate the membrane. The absence of membrane fluorescence indicates bacterial contamination, while fluorinated membranes are enough indicators of membrane free bacteria.
9:00 PM - BM2.3.03
Core-Shell NanoMOFs for CO2 Capture and Release
Safaa Alrehili 1 , Selim Beyazit 1 , Niveen Khashab 1
1 King Abdullah University of Science and Technology Thuwal Saudi ArabiaShow Abstract
Metal-Organic frameworks (MOFs), also known as coordination networks or porous coordination polymers, constitute an exciting new research area that has attracted a large amount of attention in recent years. These materials possess framework flexibility, large surface area, tailor-made framework functionalities, and tunable pore size.
In spite of their great advantages, MOFs generally have low tolerance to humidity. Recent reports have proved that MOFs could be stable in aqueous solutions and at high temperatures however, this requires the synthesis of a new class of MOFs with specific coordinating metals and ligands. Moreover, addition of certain functionalities such as surface charge, hydrophilicity/hydrophobicity etc. without deforming their excellent structure is not straightforward and demands intricate modifications. Thus, in our project we designed a novel method for coating nanoMOFs with polymeric shells by using one pot reversible addition fragmentation chain transfer (RAFT) polymerization. RAFT polymerization is one of the most facile and versatile techniques that tolerate all kinds of functionalities without losing control and livingness of polymerization. We envision that the designed system will have controlled and tailored stability depending on the nature of the polymeric shell used. Moreover, it will be used not only for CO2 capture but also controlled gas release providing a versatile platform for CO2 reuse.
9:00 PM - BM2.3.04
An on Demand Drug Delivery Depot for the Treatment of Inflammatory Arthritis
Sachin Bhagchandani 1 2 , Nitin Joshi 1 2 , Seth Levy 1 , Kai Slaughter 1 2 , Nicholas Sherman 1 2 , Praveen Vemula 1 2 , Oren Levy 1 2 , Joerg Ermann 1 , Antonio Aliprantis 1 , Jeffrey Karp 1 2
1 Brigham and Women's Hospital Cambridge United States, 2 Harvard Medical School Cambridge United StatesShow Abstract
One of the hallmarks of inflammatory arthritis (IA) is its variable disease activity with exacerbations (flares) of the chronic inflammatory joint process punctuated by periods of low disease activity. Treatment options are limited and often employ corticosteroids—agents with a plethora of toxic side effects. Use of a long acting intra-articular drug delivery method that titrates release to match disease activity would represent an attractive paradigm shift. We have developed an injectable inflammation responsive self-assembled hydrogel that can release the encapsulated drugs in response to enzymes, including matrix metalloproteinases (MMP-2 & MMP-9) and esterases, which are upregulated in inflammatory arthritis. Herein, we demonstrate the efficacy of this platform using triamcinolone acetonide (TA), a corticosteroid currently used in the clinic for the treatment of IA.
Release studies were performed in vitro to study on-demand delivery of TA in response to i) (MMP-2/ MMP-9/ esterase), ii) enzymes secreted from activated macrophages and iii) synovial fluid (SF) collected from arthritic patient's joint. TA loaded gels were evaluated in vitro for biocompatibility using chondrocytes and synoviocytes, and for anti-inflammatory efficacy using activated human macrophages. Therapeutic efficacy of TA loaded gels was evaluated in vivo using K/BxN serum model of IA developed in C57Bl/6 mice, and was compared to the therapeutic efficacy of Kenalog, the current clinically used formulation of TA.
Gels released TA in response to the enzymes that are expressed within arthritic joints (MMP-2, MMP-9 and esterases) as well as in conditioned medium of activated macrophages (Fig.1A and 1B). Incubation in PBS at 37oC released moderate amount of drug during a 50-day incubation. To evaluate on-demand delivery, enzymes were added to the release medium on day 25, which triggered the release of TA (Fig.1C). In addition, gel released TA in response to SF collected from arthritic joints, but not when incubated with normal SF (Fig.1D).
TA loaded gels showed excellent biocompatibility with both chondrocytes and synoviocytes at 20 mg/ml concentration of TA, which implies that in vivo administration of these gels will not have any detrimental effects to the surrounding cells. TA as a gel formulation demonstrated improved anti-inflammatory activity in vitro in comparison to free TA, as evident by the reduced TNF-α and increased IL-10 secretions from activated human macrophages (Fig. 2). Finally, an in vivo efficacy study showed reduced clinical scores for animals treated with TA loaded gels (20 mg TA/ml), compared to the scores observed for untreated animals and animals treated with Kenalog (20 mg TA/ml) (Fig. 3).
Overall, our results suggest that an inflammation responsive hydrogel as self-titrating drug delivery system can offer improved therapeutic benefit in inflammatory arthritis.
9:00 PM - BM2.3.05
Design of New Generation pH/Redox-Sensitive Ellipsoidal and Targeted Hybrid Nanocarriers for Triggered Delivery
Gokcen Birlik Demirel 1
1 Gazi University Ankara TurkeyShow Abstract
Cancer remains one of the world’s most devastating diseases, with more than 10 million new cases every year1. In traditional treatment methods, anti-cancer drug molecules circulate freely in the blood and do not exhibit targeted release and kill the healthy cells besides cancer cells. Because of these reasons and considering the emerging technology, the scientists from many disciplines study intensively for the development of new-generation nanocarrier systems which can do selective and controlled release2-3. Nanocarriers have many advantages compared to traditional methods. First of all, the drug molecules are trapped into the nanocarriers and the toxicity of drug can be decreased in minimum levels. Thus uncontrolled delivery can be prevented and the drug dose can be adjusted to minimum but effective levels4-5.
In this study, we have developed a novel ellipsoidal and pH/redox-sensitive hybrid nanocarrier system for triggered and targeted drug delivery applications. These multifunctional hybrid nanoparticles (Fe3O4@SiO2@PLH-PEG/PEG-FA) composed of an ellipsoidal Fe3O4 core, a mesoporous silica shell and pH/redox-responsive poly(histidine)-co-poly(ethylene glycol) (PLH-co-PEG) polymer as gatekeeper and PEG-Folic acid (PEG-FA) polymer as the targeted agent to obtain an excellent platform for anticancer drug delivery. In particular, the PLH-co-PEG gatekeeper on the surface of the hybrid nanoparticle play a key role in accommodating anticancer drug molecules in the pore of the silica shell without premature release until crosslinked polymer shell gatekeepers are cleaved by glutathione (GSH). In addition to PEG-FA polymers provide to enhance the targeted cellular uptake of the nanoparticles by cancer cells. The experimental results showed that these smart nanoparticles exhibit fast DOX release profile in the presence of 10 mM GSH, due to the reductive cleavage of intermediate disulfide bonds of PLH-PEG polymer. It can be said that this multifunctional polymer shell is active for the controlling drug molecules in-and-out of silica channels. Moreover, the ellipsoidal smart nanoparticles allowed the perfect release profile under cellular pH environment.
As a result, this study will help the development of new generation nanocarrier systems and the obtained each result from every step will be very precious to reach excellent systems in this field and will provide very big contribute to the literature.
1. Stewart, B. W., Kleihues, P. 2003. Genova, 9-11.
2. Drbohlavova, J., Chomoucka, J., Adam V., Ryvolova, M., Eckschlager, T., Hubalek, J., Kizek, R. 2013. Current Drug Metabolism, 14, 547-564.
3. Duncan, R. 2006. Nat. Rev. Cancer, 6, 688–701
4. Mishra, B., Patel, B. B., Tiwari, S. 2010. Nanomed.-Nanotechnol. Biol. Med., 6, 9-24.
5. Peer, D., Karp, J. M., Hong, S., FaroKhzad, O. C., Margalit, R., Langer, R. 2007. Nat. Nanotechnol., 2, 751-760.
This work was supported by the TUBITAK Grant No. 115R280.
9:00 PM - BM2.3.06
Synthesis and Catalytic Properties of Gold Nanoplates and Their Application for Chemiluminscent Detection of Foodborne Microorganisms
Minh-Phuong Bui 1 , Abdennour Abbas 1
1 University of Minnesota Saint Paul United StatesShow Abstract
Microbial spoilage of food has been a constant nuisance and an unavoidable problem throughout history that affects food quality and food safety in a variety of ways. A simple and rapid test of foodborne fungi and bacteria in food and environmental samples is essential for proper management of food spilage and assurance of food quality and safety. A number of different techniques have been developed for detection and enumeration of foodborne pathogens including plate counting, enzyme-linked immunosorbent assay (ELISA), polymer chain reaction (PCR), nucleic acid sensor, electrical and microscopy methods. However, the significant drawbacks of these techniques are high demand of operation skills and the time and cost involved. In this report, we introduce a rapid method for detection of bacteria and fungi in food products using a specific interaction between a reducing agent (tris(2-carboxylethyl)phosphine (TCEP)) and the microbial surface proteins. The chemical reaction was transferred to a transduction system using gold nanoplates-enhanced chemiluminescence. We have optimized our nanoplates synthetic conditions, characterized the chemiluminescence parameters and optimized conditions for the microbial assay. The new detection method was applied for rapid detection of bacteria (E.coli sp. and Lactobacillus sp.) and fungi (Mucor sp.), with limit of detection as low as single digit cells per mL within 10 min using a portable luminometer. We expect our simple and rapid detection method to be a powerful alternative to the conventional plate counting and immunoassay methods for rapid screening of foodborne microorganisms.
Keywords: foodborne pathogens, gold nanoplates, chemiluminescence, reducing agents, luminol
9:00 PM - BM2.3.07
Silicon Nanowire Based Scaffold for Optical Pacing of Cardiomyocytes
Kelliann Koehler 1 , Ramya Parameswaran 2 3 , Zhiqiang Luo 4 , Michael Burke 4 , Bozhi Tian 4
1 Chemistry University of Chicago Chicago United States, 2 Medical Scientist Training Program University of Chicago Chicago United States, 3 Biophysical Sciences University of Chicago Chicago United States, 4 University of Chicago Chicago United StatesShow Abstract
Recent developments in cardiac tissue engineering have produced a range of synthetic or biological polymer based scaffold materials with proper mechanical and biological cues for cardiomyocytes. These scaffold materials promise advancements over traditional cardiac graft materials for treatment of heart damage. Despite these advances, such scaffolds primarily served as passive supports for cardiac tissue. Here we report a silicon nanowire based scaffold with the potential for localized optical stimulation of cellular components. As an optically responsive semiconductor, the silicon nanowires can function as a stimulation platform to direct synchronous beating of cells interfaced with the scaffold. Recently, our lab has demonstrated that silicon nanostructures can provide localized optical control of cellular membrane potential in excitable cells through photothermal or photoelectric stimulations. This functionality of silicon nanostructures was used to pace primary neonatal rat cardiomyocytes seeded on fibronectin coated silicon nanowire scaffolds. Immunofluorescent staining with connexin 43 and cardiac troponin I antibodies, verified that cells grown on the nanowire scaffold were viable, aligned, and were electrically connected to neighboring cells via gap junctions. These findings demonstrate a significant advancement towards a novel platform to optimize therapeutic strategies for patients who suffer from cardiac arrhythmias as a result of cardiac tissue damage.
9:00 PM - BM2.3.08
Antibody-Functionalized Silicon Nanowires for the Depolarization of T Cells
Michael Burke 1 , Ramya Parameswaran 1 , Bozhi Tian 1 , Erin Adams 1
1 Chemistry University of Chicago Chicago United StatesShow Abstract
Interfacing electronic devices with biological systems for clinical therapeutics has been of interest for many decades now. Traditionally, many of these devices are targeted at excitable cell systems. Here, we use silicon nanowire (SiNW) technology to study the role of membrane voltage in T cell activation. Previous work in the Tian lab has demonstrated that coaxial pin SiNWs can photoelectrically elicit action potentials in neurons. More specifically, we use coaxial pin SiNWs to photoelectrically depolarize Jurkat T cell membranes. This approach offers advantages over other optical approaches for the manipulation of cellular behavior such as optogenetics, which requires gene transfection of light-activatable ion channels into the target cell. In this study we demonstrate that upon green laser stimulation of the T cell-SiNW interface for various timepoints, we can depolarize T cell membranes. We also visualize the material-T cell interface using microscopy and show that T cell viability is unaffected by the presence of the SiNWs. Using chemical surface functionalization approaches for SiNWs with antibodies specific for T cell co-receptors, we improve the binding interface between the cells and SiNWs and assess the stimulation efficiency upon the creation of this enhanced binding interface. Our work will provide us with a platform to further study how T cell membrane depolarization can alter T cell signaling upon stimulation through the T cell receptor and more broadly will serve as an important foundation for improving treatments for patients with autoimmune diseases.
9:00 PM - BM2.3.09
Redox-Sensitive Cross-Linked Fe3O4/GQDs Nanoparticles as Novel Delivery System for Cancer Treatment
Daysi Diaz 1 2 , Dayra Badillo 1 2 , Bibek Thapa 1 2 , Juan Beltran-Huarac 1 2 , Brad Weiner 1 , Gerardo Morell 1
1 University of Puerto Rico, Río Piedras Campus San Juan United States, 2 Molecular Science Research Center San Juan United StatesShow Abstract
In this study, we have developed an efficient cancer-targeted nanoplatform based on Fe3O4/GQDs nanoparticles, which was functionalized with a redox sensitive cross-linker that activates in a reducing intracellular environment ensuring the drug can be released upon cellular uptake. To endow this nanoplatform with improved specificity, the composite surface was further modified with human transferrin protein, and doxorubicin hydrochloride (DOX) providing a dual-targeted capability to deliver the drug into the cells and stimulate the generation of reactive oxygen species therein. The cell viability was measured via MTS assay and flow cytometry, and the imaging and internalization through confocal microscopy. The singlet oxygen quantum yield was also quantified. Moreover, our findings indicate that the multifunctional nanocarrier shows an excellent drug loading ability with an enhanced efficiency for photodynamic therapy and improved specificity ascribed to the disulfide bond breakage upon cell entry. This piece of research represents a step forward to designing novel alternatives for treating cancer and describes an innovative protocol for theranostics.
9:00 PM - BM2.3.10
Tunable Magnetism of Iron Oxide/Graphene Nanocomposites for Advanced MRI Applications
Bibek Thapa 1 , Daysi Diaz 1 , Dayra Badillo 1 , Emmanuel Morales 1 , Eduardo Perez 1 , Nitu Kumar 1 , Juan Beltran-Huarac 1 , Huadong Zeng 2 , Brad Weiner 1 , Gerardo Morell 1
1 Molecular Sciences Research Center University of Puerto Rico San Juan United States, 2 Advanced Magnetic Resonance Imaging and Spectroscopy Facility University of Florida Gainesville United StatesShow Abstract
Nanocomposites based on iron oxide (IO) and graphene (G) have recently emerged as novel materials for diverse applications, such as energy storage and biomedicine. Specifically, in biomedicine, the optimization of the loading amount of iron oxide nanoparticles on graphene that endows with the desired properties, has not fully investigated yet. Here, we report the optimization of loading ratio of iron oxide nanoparticles to graphene from IO:GO=1:3 to 4:3, in order to tune its magnetic as well as biological properties assessing its ability as novel MRI T2-contrast agents. Our findings indicate that the T2 relaxivity is increased by ~ 50% as the ratio of iron oxide nanoparticles is increased by 1, being ~183 mM-1s-1 the highest relaxivity recorded for IO:GO=4:3. This is attributed to the higher amount of IO content, which is responsible for producing higher susceptibility gradient in aqueous environment. The X-ray diffraction reveals that the peaks relevant to GO are attenuated as the concentration of IO increases in GO, evidencing the distortion of graphene oxide layers. The colloidal stability of this hybrid material is confirmed through dynamic light scattering (DLS) and zeta potential. The in vitro MTS assays show that cytotoxicity on HeLa, Human T lymphoblast, A549 and HepG2 cells increases for the sample of higher IO:GO ratio. The phantom imaging measurements and in vivo MRI tests will be also discussed.
9:00 PM - BM2.3.11
Enzymatically Degradable Hybrid Organic-Inorganic Bridged Silsesquioxane Nanoparticles for In Vitro Imaging
Yevhen Fatieiev 1 , Jonas Croissant 1 , Khachatur Julfakyan 1 , Lin Deng 1 , Dalaver Anjum 2 , Andrei Gurinov 2 , Niveen Khashab 1
1 Advanced Membranes and Porous Materials Center King Abdullah University of Science and Technology Thuwal Saudi Arabia, 2 Imaging and Characterization Core Laboratory King Abdullah University of Science and Technology (KAUST) Thuwal Saudi ArabiaShow Abstract
Bridged silsesquioxane (BS) nanomaterials with chemical structures O1.5Si-R-SiO1.5 where R organic groups are emerging as the next generation of organosilica nanocomposites.1 Physical and chemical properties of BS materials can be governed by the nature of homogenously distributed organic fragments within the siloxane network.2 Nonetheless, due to the synthetic challenge to control the kinetic in sol-gel processes, most non-porous BS materials that have been extensively studied in the past two decades were macroscaled.3 Ideally, for biomedical purposes BS NPs should be non-aggregated sub-200 nm nanomaterials to benefit the enhanced permeation and retention (EPR) effect and, thus, accumulate in cancerous tissues and organs. Nature-inspired oxamide bridged silsesquioxane was used as a key component to endow nanoparticles with degradable feature. For all experiments sol-gel process was applied.
The designed nanomaterials were non-aggregated with biologically relevant sizes (sub-200 nm) for preferential accumulation in tumors. The unique constitution of the materials with a very high organic content (~50%) was found to be homogenously distributed within individual particle and confirmed by various techniques: FTIR, solid state NMR and STEM-EELS elemental mapping. According to nitrogen-sorption measurements with the BET (Brunauer-Emmett-Teller) theory obtained BS NPs are nonporous with 25 m2/g surface area. The biodegradation of NPs was demonstrated in the presence of the trypsin enzymes in simulated biological media. Furthermore, nonporous fluorescent BS NPs were obtained via incorporation of fluorescein isothiocyanate moieties inside the siloxane framework in order to image cancer cells. In-vivo studies show that concentration of silicon reaches maximum in mice urine on the second day after injection of BS NPs and goes to zero on the fifth day (according ICP-MS).
We describe the first example of enzymatically degradable bridged silsesquioxanes based on oxamide bridges. The oxamide functions were incorporated via a novel bridged alkoxysilane designed to mimic the enzymatic cleavage in the human metabolism. These novel hybrid organosilica NPs can find significant interest as future biomedical applications of inorganic silica NPs require higher biodegradability.
 Chen, Y.; Meng, Q.; Wu, M.; Wang, S.; Xu, P.; Chen, H.; Li, Y.; Zhang, L.; Wang, L.; Shi, J. J. Am. Chem. Soc. 2014, 136 (46), 16326-16334.
 Hu, L.-C.; Shea, K. J. Chem. Soc. Rev. 2011, 40 (2), 688-695.
 Creff, G.; Pichon, B. P.; Blanc, C.; Maurin, D.; Sauvajol, J. L.; Carcel, C.; Moreau, J. J.; Roy, P.; Bartlett, J. R.; Man, M. W.; Bantignies, J. L. Langmuir 2013, 29 (18), 5581-5588.
9:00 PM - BM2.3.12
Nanoparticle-Based Periodontitis Antimicrobial Photodynamic Therapy
Laura de Freitas 1 , Giovana Calixto 1 , Marlus Chorilli 1 , Jucaira Giusti 2 , Vanderlei Bagnato 2 , Nikolaos Soukos 3 , Mansoor Amiji 4 , Carla Fontana 1
1 Faculty of Pharmaceutical Sciences Sao Paulo State University Araraquara Brazil, 2 Physics Institute of Sao Carlos University of São Paulo Sao Carlos Brazil, 3 Applied Molecular Photomedicine Laboratory The Forsyth Institute Cambridge United States, 4 Department of PharmaceuticalSciences School of Pharmacy, Bouvé College of Health Sciences, Northeastern University Boston United StatesShow Abstract
Antimicrobial photodynamic therapy (aPDT) is increasingly being explored for treatment of periodontitis. Here, we investigated the effect of aPDT on human dental plaque bacteria in suspensions and biofilms in vitro using methylene blue (MB)-loaded poly(lactic-co-glycolic) (PLGA) nanoparticles (MB-NP) and red light at 660 nm. The effect of MB-NP-based aPDT was also evaluated in a clinical pilot study with 10 adult human subjects with chronic periodontitis. Dental plaque samples from human subjects were exposed to aPDT - in planktonic and biofilm phase - with MB or MB-NP (25 µg/mL) at 20 J/cm2 in vitro. Patients were treated either with ultrasonic scaling and scaling and root planing (SRP) or ultrasonic scaling + SRP + aPDT with MB-NP (25 µg/mL and 20 J/cm2) in a split-mouth design. In biofilms, MB-NP eliminated approximately 25% more bacteria than free MB. The clinical study demonstrated the safety of aPDT. Both groups showed similar improvements of clinical parameters 1 month following treatments. However, at 3 months ultrasonic SRP + aPDT showed a greater effect (28.82%) on gingival bleeding index (GBI) compared to ultrasonic SRP. The utilization of PLGA nanoparticles encapsulated with MB may be a promising adjunct in antimicrobial periodontal treatment.
9:00 PM - BM2.3.13
Magnetic Microcapsules for Delivery of microRNA
Samantha Gabriel 1 2 , Gleb Sukhorukov 1 2 , Nicholas Peake 3
1 Queen Mary University of London Institute of Bioengineering London United Kingdom, 2 Queen Mary, University of London School of Engineering and Material Science London United Kingdom, 3 Sheffield Hallam University Biomolecular Research Centre Sheffield United KingdomShow Abstract
Delivering microRNA is a conceivable new treatment for many diseases, however, in vivo extremely difficult. Therefore a delivery system, like microcapsules, is required. Microcapsules are containers, of less than 5μm in size, created by layer-by-layer formation. This process allows for precise control of the protective polymer shell and for the imbuing of targeting functionalities.
Many bioactive molecules can be functionally delivered intracellularly using microcapsules and have proven to be suitable vectors in vivo. This project aims to functionally deliver microRNA (miRNA) using magnetically-targeted microcapsules in vitro, which has not been previously demonstrated.
In many diseases, namely cancer, changes in miRNA levels results in detrimental changes in multiple downstream protein targets, this then leading to disease progression. Therefore, the rationale behind this therapeutic is to normalise these deficiencies by delivering mimics of the insufficient miRNA or miRNA antagonist to obstruct a surplus of miRNA.
This work focuses on miR-19a mimics and miR-19a antagonists being delivered using degradable magnetic microcapsules to colorectal cancer cells. miR-19a is responsible for mediators of cancer progressions. Interestingly, efficient delivery of miR-19a antagonists is challenging even in vitro with traditional techniques.
Encapsulation of miR-19a in magnetic microcapsules has been a success. Also Confocal Fluorescent Microscope images showing cell internalisation and consequent release of miRNA strongly prove that microcapsules are delivering miRNA. These images also confirmed effective targeting using a magnet. New data showing effectiveness of the miRNA-microcapsules in influencing downstream protein expression will be presented. Following successful manipulation of protein expression, miRNA-microcapsules will be tested in an in vivo model.
9:00 PM - BM2.3.14
One-Pot Preparation of Dual-Drug Loaded Antibody Functionalized Amphiphilic Chitosan Nanoparticles with Enhanced Synergistic Effect towards Lung Cancer Stem Cells
Wei-Ting Huang 1 , Dean-Mo Liu 1 , Mikael Larsson 2
1 Materials Science and Engineering National Chiao Tung University HsinChu Taiwan, 2 Future Industries Institute Mount Gambier AustraliaShow Abstract
Multi-drug resistance (MDR) in stem-like cancer cells, also known as cancer stem cells, is emerging as a reason for failed treatment and cancer relapse. This work was conducted under the hypothesis that a one-pot synthesis could prepare targeted, biodegradable, dual-drug loaded nanoparticles, for intracellular co-delivery of a highly effective anticancer drug and a drug that inhibit the MDR-pathways. The commonly used and effective anti-cancer drug cisplatin (CDDP) and the Chinese herbal extract demethoxycurcumin (DMC) were loaded in biodegradable carboxymethyl-hexanoyl chitosan (CHC) nanoparticles targeted for CD133 antigen, which is often overexpressed on the membrane of stem-like cancer cells. The system was evaluated in vitro using stem-like A549-ON lung cancer cells with excellent results. Co-delivery of the drugs using the CHC nanoparticles achieved greatly enhanced efficacy at lowered drug concentration compared to free dual-drugs or individual drugs in nanoparticles, the targeting improved the efficacy even further. This significant result highlighted that CHC successfully synergized the effects of DMC and CDDP. The ease of preparation, biodegradation and biocompatibility of the CHC and the excellent in vitro results against stem-like cancer cells makes the system highly promising and realistic as a nanomedical approach to overcome MDR in cancer treatment. However, further demonstration of performance in vivo is needed and will be the next step towards clinical realization of the concept.
9:00 PM - BM2.3.15
Directional Clustering of Anisotropic Bimetal-Polymer Composite Nanostructures for
Surface Enhanced Raman Scattering-Based Biosensing
Eun Young Hwang 1 , Dong Woo Lim 2
1 Department of Bionanotechnology, Hanyang University Ansan Korea (the Republic of), 2 Department of BioNano Engineering and Department of Bionanotechnology, Hanyang University Ansan Korea (the Republic of)Show Abstract
Controlled self-aseembly of anisotropic nanostructures has made great advances in nanomaterials and nanophotonics. An anisotropic inorganic-organic composite nanostructure with multi-compartments has different functionalities and physicochemical characteristics at each compartment, and their directional assembly formed via covalent- or noncovalent interactions induces unique optical properties, which can be applied to a variety of photonics-based biosensing applications. Especially, surface-enhanced Raman scattering (SERS) has been of great importance for biochemical detection because it has ultra-high sensitivity, narrow bandwidth as well as significant multiplexing capabilities. In this study, we report that anisotropic bimetal-polymer composite nanostructures were formed via oxidation-reduction, and were directionally clustered into forming superparticular structures composed of bimetal core and polymer shell via noncovalent interaction. The aniline monomers were surface-templated polymerized into poly(aniline) by reducing silver nitrate in the presence of a surfactant so that poly(aniline) and reduced silver were eccentrically deposited onto a variety of Au seeds with different physical dimensions, providing both bimetallic Au core - Ag shell compartment and poly(aniline) counter-compartment of the anisotropic composite nanostructures. Moreover, a variety of anistropic bimetal-polymer nanostructures were prepared by introducing various ligands or polymers onto metallic seeds, and they were directionally clustered via noncovalent interaction by selective surface modification of the bimetallic compartments, exhibiting significant enhancement of optical properties due to increased electromagnetic field in the interstices between them. As a proof of concept that these anisotropic bimetal-polymer composite nanostructures would be potential SERS nanoprobes for biosensing, we demonstrated the formation of sandwich-type immunocomplexes composed of SERS nanoprobes and magnetic beads in the presence of target proteins, and showed SERS-based quantitative analysis with a linear correlation between relative Raman intensity and concentration of the target proteins. Conclusively, these anisotropic composite nanostructures and directional clusters would be promising as advanced functional nanoprobes for SERS-based biosensing applications.
9:00 PM - BM2.3.16
Antibacterial Activities of Gold-Coated Silver Nanoparticles on Pathogenic Bacteria
Hiroaki Ichimaru 1 , Takayuki Kawagoe 1 , Ayaka Harada 2 , Katsuhiko Ono 3 , Hiroyasu Tsutsuki 3 , Tomohiro Sawa 3 , Shigeru Morimura 1 , Takuro Niidome 1
1 Faculty of Advanced Sciences and Technology Kumamoto University Kumamoto City Japan, 2 Department of Applied Chemistry and Biochemistry Kumamoto University Kumamoto City Japan, 3 Department of Microbiology, Graduate School of Medical Sciences Kumamoto University Kumamoto City JapanShow Abstract
Silver nanoparticles are known to have antibacterial property. However, these nanoparticles are unstable and tend to form aggregates. To improve the stability of nanoparticles in aqueous medium and to apply the nanoplates as an anti-bacterial material, we developed triangular and plate-shaped silver nanoparticles (silver nanoplates) coated with gold atoms and then evaluated their dispersion stabilities and antibacterial activities on some pathogenic bacteria including Salmonella enterica serovar Typhimurium.
We evaluated antibacterial activities of silver nanoplates without gold coat (Ag NPLs) and those coated with one to four layers of gold atoms (Ag@Au1L NPLs, Ag@Au2L NPLs, Ag@Au4L NPLs) by colony-forming unit assay on LB agar plate. Ag NPLs and Ag@Au1L NPLs showed antibacterial activities. Surprisingly, addition of fetal bovine serum to LB medium enhanced the antibacterial activities. Furthermore, Ag@Au1L NPLs showed the strongest activity in this condition. We hypothesized that some components of the serum adsorbed on surface of the nanoplates and contributed to its stability in LB medium. Furthermore, concerning stability in LB medium, we examined changes in absorption spectrum, distribution of particle size and zeta potential of the NPLs in LB medium with or without serum. In the case of Ag@Au1L NPLs, there would be some defects on gold layer, and the silver atoms would be released as silver ions from them. Meanwhile, for Ag@Au2L NPLs and Ag@Au4L NPLs, silver ions would not release from inside because of thick gold layer.
9:00 PM - BM2.3.17
Photocleavable Hydrogel-Coated Upconverting Nanoparticles as Multifunctional Platform for NIR Imaging and On-Demand Macomolecular Delivery
Ghulam Jalani 1
1 McGill University Montreal CanadaShow Abstract
Loaclized and recurring delivery of drugs is of great importance in many medical conditions such as in the treatment of solid tumors, localized infections and post-surgical wounds. Triggerable drug delivery platforms are often created from materials that undergo physical or chemical change in their structure when exposed to certain environmental stimuli such as light, temperature, pH, electric/magentic fields and enzymes etc. Among them, light stands out as potential candidate due to its non-invasiveness, high temporal resolution and ability to be controlled remotely. However, light-controlled systems have inherent problem: UV and Vis wavelength is required to initiate the photoreaction. Both of these lights are unable to penentrate beyond few millimeters in the body. An alternative is the use of near infrared (NIR) light since biological tissues are transparent to NIR wavelenghths. However, photoactive materials do not respond to this light. Lanthanide-doped upconverting nanoparticles (UCNPs) have emerged as excellent transducers for converting longer wavelength near-infrared (NIR) light to shorter wavelengths spanning the UV to the Vis regions of the spectrum via a multiphoton absorption process, known as upconversion. Here, we report the development of NIR to UV–Vis–NIR UCNPs consisting of LiYF4:Yb3+/Tm3+@SiO2 individually coated with a 10 ± 2 nm layer of chitosan (CH) hydrogel cross-linked with a photocleavable cross-linker (PhL). We encapsulated fluorescent-bovine serum albumin (FITC-BSA) inside the gel. Under 980 nm excitation, the upconverted UV emission cleaves the PhL cross-links and instantaneously liberates the FITC-BSA under 2 cm thick tissue. The release is immediately arrested if the excitation source is switched off. The upconverted NIR light allows for the tracking of particles under the tissue. Nucleus pulposus (NP) cells cultured with UCNPs are viable both in the presence and in the absence of laser irradiation. Controlled drug delivery of large biomolecules and deep tissue imaging make this system an excellent theranostic platform for tissue engineering, biomapping, and cellular imaging applications.
9:00 PM - BM2.3.18
Cyclodextrin-Graphite Oxide-Carbon Nanotube Composites for Electrochemical Supramolecular Recognition
Hae Kyung Jeong 1
1 Daegu University Gyeongsan Korea (the Republic of)Show Abstract
Three different size of cyclodextrin (α, β, and γCD) is used in the synthesis of cyclodextrin-graphite oxide-carbon nanotube (CD-GO-CNT) composites and compared for the electrochemical supramolecular recognition. All composites show very good electrochemical response to three biomolecules (dopamine, ascorbic acid, and thioridazine), and the response of the electrical current is linearly proportional to the concentration of the biomolecules. Bigger size of CD composite is more sensitive, resulting that αCD-, βCD-, and γCD-GO-CNT composites are in the order of the increasing sensitivity to the response. γCD-GO-CNT composite, therefore, gives the best electrochemical supramolecular recognition performance among the other composites because of the biggest cavity of γCD (0.95 nm of diameter) compared to αCD (0.57 nm of diameter) and βCD (0.78 nm of diameter), and detail results will be discussed.
9:00 PM - BM2.3.19
Enhanced Antimicrobial Effect of Metal Oxide-Based Nanoparticles on Escherichia Coli and Bacteriophage
Hyo-Eon Jin 1 , Su-Eon Jin 2
1 Ajou University Suwon Korea (the Republic of), 2 Inha University Incheon Korea (the Republic of)Show Abstract
Disinfection and implementation of new effective methods for sanitary practice are critical steps for health care. Metal oxides have been studied to overcome the limitations of current antimicrobial treatment like antibiotic resistance. In general, they have an antimicrobial activity based on the release of their ions and the induction of oxidative stresses via the generation of reactive oxygen species (ROS). Their antimicrobial activities are also associated with sorption potential to micro-organisms which may be related to the species-based sensitivity of metal oxides. In this study, we screened the metal oxides-based nanoparticles to have an enhanced antimicrobial effect on Escherichia coli (E. coli) and bacteriophage (phage). Zinc oxide-, magnesium oxide-, and copper oxide-based nanoparticles were used to evaluate their antimicrobial activities. First, their size, surface area and crystallography were monitored using a light scattering, BET analysis and x-ray diffraction. Morphology of metal oxide-based nanoparticles was determined using a scanning electron microscopy. For their antimicrobial activity tests, nanoparticles were added to culture medium and their dose-responses were characterized. Their combinations of nanoparticles were also tested, and measured the microbial activity against E.coli and phage. Nanoscale sized metal oxides with a high sorption capacity were confirmed. Zinc oxide-, magnesium oxide-, and copper oxide-based nanoparticles showed cytotoxicity on E. coli and phage in a dose-dependent manner. Combination of metal oxide-based nanoparticles also showed a strong antimicrobial effect. Our results demonstrate that metal oxide-based nanoparticles have a potential to be extensively used as antimicrobial agents. We anticipate that metal oxide-based nanoparticles can be applied for various disinfection steps in pharmaceutical industry and water purification systems.
9:00 PM - BM2.3.20
Development of Safety Assessment Technique for Nano-Materials by Using Planarian
Shigetaka Katori 1 , Takanobu Maezawa 1 , Kazuaki Hiroki 1 , Norito Shibata 1
1 National Institute of Technology Tsuyama JapanShow Abstract
Accelerating developments in the science and technologies afford modern civilization, however, simultaneously producing many kinds of material that cannot be degraded in natural environment. Development of evaluation methods and systems of the safety of nano-materials are urgently needed. However, it is extremely hard to confirm toxicity of the each nano-materials with different shapes and chemical structures.
We pay attention to primitive animal planarians, because they have tremendous vital power. For example, if they were cut down to small pieces, it can be regenerated from the all pieces. This distinguishing characteristic is based on pluripotent stem cell. In addition, planarian has primitive brain and regenerative capability. Therefore, they have very similar biological functions with higher animals including a human.
In order to discuss effects of toxicity of semiconductor materials to planarians, we produced foods that were combined organic semiconductor materials such as methyl ammonium lead- halide which used for solar cells. For preparing of the foods, the concentration ratio of the semiconductor material were changed. And then we gave the three different concentration foods to 20 planarians for one month, after that morphological observation was perform.
The results obtained from morphological observation, we found that the number of eyes of some individuals has changed. Generally, lead is known to affect the biological nervous system. However, whether the influence of the semiconductor material, it is necessary to further detailed examination.
9:00 PM - BM2.3.21
Fluorescent Nanosensor for Ratiometric Imaging of Intracellular Calcium
Eric Kim 1 , Guoxin Rong 1 , Heather Clark 1
1 Northeastern University Boston United StatesShow Abstract
Optode-based nanosensors have been widely implemented as tools for visualizing and monitoring of targeted ions and biomolecules. Here, we describe an improved optical ion sensor called calcium polymer-free nanosensor (CaPFN) for detection of free and elevated nanomolar calcium levels in living cells. The CaPFN is comprised of a plasticized matrix embedded with optode sensing chemistry and fluorescent dyes to selectively image calcium ion concentrations. Ratiometric fluorescent measurements show that CaPFNs are selective for calcium ions over magnesium by 4 orders of magnitude, exhibit a fully reversible response, and respond to a nanomolar dynamic sensing range both in solution and in the intracellular environment. For detection of intracellular calcium transients, nanosensors are delivered into the cell cytoplasm and their responsiveness to drug-evoked calcium store release are demonstrated by live-cell confocal microscopy. Overall, the newly optimized CaPFNs offer a new tool for optical determination of intracellular calcium, and demonstrate a new platform for detection of other target ions such as sodium and chloride, owing to its modular design and ease of preparation.
9:00 PM - BM2.3.22
Multifunctional Endoscope System with Theranostic Nanoparticles and Bio-Electronics for Colon Cancer Treatment
Changyeong Song 1 2 , Dae-Hyeong Kim 1 2 , Taeghwan Hyeon 1 2
1 Center for Nanoparticle Research Institute for Basic Science Seoul Korea (the Republic of), 2 School of Chemical and Biological Engineering Seoul National University Seoul Korea (the Republic of)Show Abstract
Endoscopes have been used to detect polys, bleeding and other abnormalities in the gastrointestinal tract. The endoscopes contain imaging tools and therapeutic devices together for effective cancer treatment. However, current endoscope system has a limitation in small cancers detection and long treatment time. Here, we developed a multifunctional endoscope system that consists of transparent bio-electronics and theranostic nanoparticles to overcome these problems. Bio-electronics can sense the change of temperature, pH, and impedance for detecting the colon cancer. Bio-electronics enables radio frequency ablation for treating the large-size cancer lesions. Theranostic nanoparticles can do fluorescence imaging and photo-triggered therapy. In-vitro, ex-vivo, and in-vivo experiments show that the endoscope system can be the closed-loop solution for colon cancer treatment.
9:00 PM - BM2.3.23
Silica-Based Surface Modification of Food Processing and Handling Gloves for Food Safety and Healthcare Environment
Jun Oh 1 , Luis Cisneros-Zevallos 1 , Mustafa Akbulut 1
1 Texas Aamp;M University College Station United StatesShow Abstract
Gloves made of materials such as latex, nitrile, and polyethylene are the most common types of protective equipment used to prevent cross-contamination and transmission of pathogenic bacteria in the food industry. In this study, we report a surface modification approach involving “fluorinated silica nanoparticles” (FSNs) to improve the protective ability against bacterial contamination of disposable glove surfaces. The bacterial antiadhesive (antifouling) properties of the modified gloves were evaluated with Salmonella Typhimurium LT2 and Staphylococcus aureus at bacterial concentrations of 8.6-9.0 log CFU/mL through the dip-inoculation approach. Bacterial attachment to glove surfaces were enumerated by the pour plating method as well as direct counting via scanning electron microscopy. The bacterial populations of S. Typhimurium LT2 and S. aureus on FSN-coated latex, nitrile and polyethylene gloves was reduced by 1-2 log units in comparison to bare gloves, which already reduce the bacterial attachment to some extent.
9:00 PM - BM2.3.24
Cellular Uptake Dynamics of Label Free Silicon Nanowires
John Zimmerman 1 , Graeme Murray 1 , Yucai Wang 1 2 , Ramya Parameswaran 1 , Bozhi Tian 1
1 University of Chicago Chicago United States, 2 School of Life Sciences and Medical Center University of Science amp; Technology of China Hefei ChinaShow Abstract
Nanoscale semiconductors are an important class of materials for use as biosensors, drug delivery carriers, and engineered tissue scaffolds, with silicon nanowires (SiNWs) being of particular interest because of their potential cytocompatibility, and their ability to be rationally designed, providing precise control over the devices structural and material properties. These unique characteristics make them an ideal material for designing a wide range of nanoscopic 'building blocks' which can be applied in a biological context. As an example of this, we recently demonstrated how kinked SiNWs can be used as both intra- and intercellular force probes for studying cell behavior. Despite these advances, there is still much to be understood about the bio-interface of these materials. For instance, a careful examination is still needed of how these large inorganic nanoconstructs can be internalized. Here we demonstrate that label free SiNWs can be internalized in multiple cell lines (~96% uptake rate), and that once internalized they undergo an active 'burst-like' transport process. Our results suggest that rather than through exogenous manipulation, SiNWs are internalized primarily through an endogenous phagocytosis pathway. To study this behavior we have developed a robust set of methodologies for quantitatively examining high-aspect ratio nanowire-cell interactions in a time-dependent manner, on both the single cell and ensemble levels. This approach represents one of the first dynamic studies of semiconductor nanowire internalization and offers valuable insight into designing devices for bio-molecule delivery, intracellular sensing and photoresponsive therapies.
9:00 PM - BM2.3.25
Antibacterial Activity of ZnO Nanoparticles Embedded into Coaxial Polycaprolactone Electrospun Fibers
Gina Prado-Prone 1 2 3 , Phaedra Silva-Bermuedez 2 , Jorge Alfonso Garcia Macedo 3 , Argelia Almaguer Flores 4 , Clemente Ibarra 2 , Cristina Velasquillo-Martinez 2
1 National Autonomous University of Mexico Distrito Federal Mexico, 2 National Institute of Rehabilitation Distrito Federal Mexico, 3 National Autonomous University of Mexico Distrito Federal Mexico, 4 National Autonomous University of Mexico Distrito Federal MexicoShow Abstract
We developed coaxial electrospun core-shell fibers of polycaproactone (PCL) in the inner core and PCL with zinc oxide (ZnO) nanoparticles (NPs) in the outer shell. Fibers were fabricated as an alternative antibacterial dressing to prevent infections during the treatment of dermal injuries. Antibacterial studies of inorganic NPs have become important due to the increased bacterial resistance against antibiotics. We used ZnO NPs (~25nm), which are chemically stable and possess an excellent photocatalytic property. ZnO NPs are low-cost material, listed as a “generally recognized as safe” (GRAS) by Food and Drug Administration (FDA). ZnO NPs have shown antibacterial activity (ABA) against a broad spectrum of bacterial strains attributed to two mechanisms: 1) Photocatalysis; i.e ZnO NPs in aqueous solution under UVA radiation produce reactive oxygen species (ROS) which penetrate the cell membrane; 2) Release of Zn+2 ions, which in high concentration adhere to cell membranes. Both mechanisms causing bacterial death and occur on NPs surface. On the other hand, the application of inorganic NPs in medical treatment is limited because of the possible long-term side effects that might be caused by NPs release. In this study, ZnO NPs were dispersed into PCL electrospun fibers to prevent its release. The antibacterial effect of the ZnO NPs/PCL fibers have already been reported (1); however, the ZnO NPs were dispersed across the whole fibers and thus NPs in the center of the fiber did not participate in the ABA. In order to optimize the use of ZnO NPs concentration in PCL fibers, we developed core-shell coaxial electrospun fibers where the core of the fibers corresponded to PCL and the shell to mixture of PCL with ZnO NPs. In this way, ZnO NPs were only dispersed on the surface of the fibers increasing its use efficiency by means of superficial contact area. We evaluated the ABA against Escherichia coli at different concentrations of ZnO NPs embedded into uniaxial and coaxial PCL electrospun fibers under two different pre-illumination conditions: UVA light and sunlight. Preliminary results suggest that the ABA increases when ZnO NPs are only dispersed on the outer shell of coaxial fibers, indicating the potential to enhanced the ABA in coaxial fibers using the same amount of NPs than in uniaxial fibers. However, there were not significant differences in ABA between fibers under the UVA light and sunlight pre-illumination conditions. All fibers were characterized in their morphology, chemical composition, water wettability and crystalline structure by means of scanning electron microscopy, infrared spectroscopy, energy dispersive X-ray spectroscopy, X-ray photoelectron spectroscopy, X-ray diffraction and water contact angle. The coaxial electrospun fibers of ZnO NPs/PCL have a potential to be an antibacterial dressing.
(1). R. Augustine, H. Nanda, D. K. Singhal, A. Mukherjee, D. Malakar, N. Kalarikkal, S. Thomas. J. Polym. Res, (2014), 21:347.
9:00 PM - BM2.3.26
Versatile Multi-Stage Particle System for Targeted and Triggered Drug Delivery
Fabian Starsich 1 , Christoph Blattmann 1 , Sotiris Pratsinis 1
1 ETH Zurich Zurich SwitzerlandShow Abstract
The specific targeting of diseased sites with therapeutic agents is considered as a key problem in medicine. A delivery ratio of only 0.01 to 0.1‰ of an injected drug molecule is estimated. The process of specific targeting can be separated into different stages, which demand different properties from the applied therapeutic system. Multi-stage delivery particles are promising candidates to fulfill these requirements. They consist of a micrometer sized carrier particle loaded with nanometer sized cargo. In this work, advanced multi-stage delivery particles are produced via scalable flame spray pyrolysis and spray drying. Heat responsive polymer microparticles are loaded with highly superparamagnetic Zn0.4Fe2.6O4 nanoparticles and a therapeutic drug. During magnetic hyperthermia with the nano Zn-ferrites the temperature sensitive carriers can release the drug on demand. This effect was evaluated thoroughly and compared to literature. Furthermore, by optimizing shape and size of the system the targeting efficiency was evaluated ex vivo in a flow cell, showing the enormous potential of the produced particle system.
9:00 PM - BM2.3.27
Synthesis of Copper Nanoparticle Impregnated Activated Carbon for Demonstrating Water Disinfection
Pritam Biswas 1 , Rajdip Bandyopadhyaya 1
1 Indian Institute of Technology Bombay Mumbai IndiaShow Abstract
Availability of safe drinking water is of paramount importance. For this purpose, activated carbon (AC) bed is widely used as a water purification medium, which although removes most of the contaminants, however is incapable of killing pathogens. To resolve this issue, antibacterial property of copper nanoparticles (Cu-NPs) have been utilized. Therefore, the present work explores the potential of combining Cu and AC to demonstrate the application of Cu-NP impregnated AC for water disinfection in a continuous, flow-column set-up.
To this end, Cu-NPs with a mean diameter of 6.11 nm were synthesized successfully using a green synthesis method and it was successfully impregnated in plasma treated AC with 2.1 wt. % of Cu in the Cu-AC. In batch mode experiments, on using 8 mg/ml of Cu-AC, an initial E. coli cell concentration of 104 CFU/ml was reduced to zero cells within 10 minutes. The experimental data fits well with an exponential decay curve of cell concentration, with a rate constant k = 0.757 min-1. From this batch data, the maximum flow rate that could be maintained in a column (with 8 cm diameter and 25 cm height) for complete decontamination of water was calculated. A continuous flow-column (packed with only Cu-AC) showed zero cell count in the outlet water, when a contact time of 9 minutes (between E. coli and Cu-NP) was provided at a flow rate of 4.13 L/h, thereby successfully treating almost 694 L of contaminated water over an uninterrupted 7 day period. Simultaneously, in steady state continuous flow-column experiments, the maximum copper concentration in the outlet water was only about 83.4 µg/L, which is far below the upper recommended limit of 1000 µg/L (EPA).
Hence, water disinfection for potable quality water (zero E. coli count and < 1000 µg/L Cu) can be achieved in a continuous manner, with our packed Cu-AC column, with most of the Cu left intact (99.2 wt.% of total Cu loaded) in the Cu-AC hybrid for its continued, unabated performance over a long duration.
Niveen Khashab, KAUST
Jean-Olivier Durand, Université Montpellier
Jeffrey Zink, Univ of California-Los Angeles
BM2.4: Gold and Carbon-Based Systems
Luisa De Cola
Tuesday AM, November 29, 2016
Hynes, Level 1, Room 103
9:00 AM - *BM2.4.01
Surface Engineering of Gold Nanorods for Biology
Catherine Murphy 1
1 University of Illinois at Urbana–Champaign Urbana United StatesShow Abstract
Gold nanorods are virus-sized objects that exhibiti brilliiant colors in the visible and near-infrared portions of the electromagnetic spectrum. The aspect ratio of the rods governs their maximum wavelengths of absorption and scattering. The surface chemistry of these nanorods greatly influences how biomolecules and even cells respond to these materials. In this talk I will describe recent results from our lab that involve molecular-level understanding of the nano-bio interface, as well as results that show that these nanorods can influence cell behavior.
9:30 AM - BM2.4.02
Biocompatible Nitrogen-Doped Carbon Nanodots for Cancer Theragnosis
Woosung Kwon 1
1 Sookmyung Women's University Seoul Korea (the Republic of)Show Abstract
Multifunctional nanoparticles have been widely investigated for biomedical applications, such as imaging, therapy, and drug delivery. Especially, photo-activated nanoparticles have received great attention as theranostic agents because of their heat-generating abilities after exposure to laser irradiation. However, photostability and safety issues have been the technical hurdles for further clinical applications. In this regard, carbon nandots (Cdots), a class of paracrystalline carbon nanostructures, have been the subject of extensive research because of their excellent biocompatibility, innocuousness, and photostability. They are known to have a structure that some sp2 carbon clusters are embedded in a heterogeneous sp3 carbon matrix, presumably due to relatively “cold” reaction temperature, definitely insufficient to give a pure sp2 carbon structure or carbon crystal. Here, we designed nitrogen (N)-doped Cdots (N-Cdots), which have strong absorption in the near-infrared region, high photostability, and excellent biodegradability. Optimized N-Cdots can be utilized not only as a new photoacoustic (PA) imaging agent but also as a superior photothermal therapy (PTT) agent in vivo because of their strong optical absorption at a specific wavelength. We used N-Cdots to perform in vivo/ex vivo noninvasive PA imaging of sentinel lymph nodes via local delivery and performed PTT for cancer ablation therapy. Finally, biodegradation and renal clearance were confirmed by performing whole-body PA monitoring and a degradation test.
9:45 AM - BM2.4.03
Multifunctional Nanoparticles for Cancer Targeting, Detection and Chemo-Photothermal Therapies
Qingwen Guan 1 , Min Wang 1
1 Mechanical Engineering University of Hong Kong Hong Kong Hong KongShow Abstract
Theranostics, which are nanoparticles (NPs) capable of cancer detection and treatment, have attracted much attention in recent years. In this investigation, a new type of theranostics based on multifunctional NPs was designed using a combination of different nanostructured materials and then fabricated. Their characteristics and performance were subsequently studied. Compared to their spherical counterparts, gold nanorods (AuNRs) are promising agent for photothermal therapy. Using the capping surfactant CTAB present on the AuNR surface as the template for mesoporous silica formation, a mesoporous silica coating can be made on AuNRs so as to improve the functionality and biocompatibility of AuNRs. Surface enhanced Raman scattering (SERS), which involves strong enhancement of Raman scattering from molecules adsorbed on nanostructured metal surface, can be used as a highly sensitive method for cancer detection. Therefore, based on our previous studies, we developed a facile method to fabricate Au capped AuNR core-mesoporous silica shell (AuNR@mSiO2@Au) NPs, which are expected to not only provide sensitive SERS detection but also combine cancer targeting, imaging and drug delivery and photothermal therapy in a single system. Specifically, a modified seed-mediated method using binary surfactants was employed for AuNR synthesis. AuNRs were then covered by a mesoporous silica shell in a sol-gel and template removal process. Fine Au nanospheres were deposited on the outer surface of AuNR@mSiO2 NPs via electrostatic absorption. The Au nanospheres formed copious hot spots for AuNR@mSiO2@Au NPs for achieving strong SERS signals from Raman reporter molecules (rhodamine 6G) incorporated in the NPs. Furthermore, folic acid was conjugated onto AuNR@mSiO2@Au NPs, allowing them to target folate receptor-overexpressed cancer cells. Doxorubicin hydrochloride (DOX) was loaded into mesopores of NPs as a model anticancer drug. Hela cells which overexpress folate receptor were used in in vitro investigations with MCF-7 cells for control studies. The morphology, structure and composition of AuNR@mSiO2@Au NPs were studied. Drug release from mesoporous channels of AuNR@mSiO2@Au NPs was investigated. Dark-field and fluorescent microscopies were used to assess targeting and imaging capabilities. In vitro SERS signals with targeted cells were measured using Raman spectroscopy. The combined chemo-photothermal effect by AuNR@mSiO2@Au NPs was investigated after laser irradiation. The highly reduced cell viability after near-infrared laser irradiation suggested that the multifunctional nanoparticles could provide effective photothermal effect and control the release of loaded anticancer drug, thereby achieving chemo-photothermal therapies.
10:00 AM - BM2.4.04
Hydrogel/Carbon Nanotubes Nanocomposites for the Electrostimulated Transdermal Delivery of Insulin
Jean-Francois Guillet 1 , Muriel Golzio 2 , E. Flahaut 2
1 Paul Sabatier University Toulouse Cedex 9 France, 2 Centre National de la Recherche Scientifique Toulouse FranceShow Abstract
According to the statistics of the Centres for Disease Control and Prevention in the USA, more that 21 million people are diagnosed with diabetes in the USA, while more than 8 million are expected to be undiagnosed . The situation is even worse in Europe, with 55 million people diagnosed, as claimed by the World Health Organisation .
Among the very important parameters for a successful treatment is the regularity of the injection of insulin. Although pumps are available on the market for many years, most people still use needles for the subcutaneous injection of insulin. However, the use of needles is painful for the patient, and may be a problem especially for children.
We report here the realization of a nanocomposite material composed of a hydrogel of biocompatible polymer matrix and double-walled carbon nanotubes (DWCNTs) added for enhancement of both mechanical and electrical properties. This nanocomposite is loaded with a solution of insulin and allows transdermal delivery through the skin by electro-stimulation, aiming at avoiding injections and thus improving the life quality of patients. Passive crossing of the skin is possible only for small molecules so in order to make possible the transdermal delivery of a large molecule such as insulin, the permeability of the skin must be increased. This is possible using electrical stimulation, known as electropermeabilisation. For such an application, a suitable material should be both electrically conducting and having a very large specific surface area (m2/g) in order to both store the insulin and be useful for electropermeabilisation. Carbon nanotubes (CNTs), and especially double-walled CNTs (DWNTs)  are an ideal candidate and combine a good electrical conductivity with a very high specific surface area (ca. 1000 m2/g) and good biocompatibility when included in a material or deposited on a surface . Of course, toxicity aspects are largely included in in order to evaluate potential risks.
The preparation of the nanocomposite material as well as our first results of electrostimulated transdermal delivery using an ex vivo mouse skin model will be presented.
 E. Flahaut, R. Bacsa, A. Peigney, Ch. Laurent, "Gram-Scale CCVD Synthesis of Double-Walled Carbon Nanotubes", Chem. Commun., (2003), 1442-1443
 A. Béduer, F. Seichepine, E. Flahaut, I. Loubinoux, L. Vaysse, Ch. Vieu, "Elucidation of the role of carbon nanotube patterns on the development of cultured neuronal cells", Langmuir, 28, (50), (2012), 17363–17371
10:15 AM - BM2.4.05
Mechanism of Heat Generation by Gold Nanoparticle Colloids in Radiofrequency Field
Tatsiana Mironava 1 , Sergey Suchalkin 1 , Visal Thalawe Arachchilage 1
1 Stony Brook University Stony Brook United StatesShow Abstract
Gold nanoparticles (AuNPs) have a great potential in various biomedical applications such as imaging techniques, drug delivery, and gene therapeutic. They are also being explored as agents for radiofrequency ablation (delivering heat) to malignancies due to their stability, low toxicity and easiness of conjugation for targeted delivery. Unlike chemotherapeutic agents, AuNPs have no side effects because they are harmless unless activated inside of the tumor by the energy source, such as a near-infrared (IR) light or radiofrequency (RF) waves. Currently several types of IR-activated AuNPs are being tested in human clinical trials for the treatment of cancer. There are no clinical studies on RF-activated AuNPs, however, such particles have a significant advantage since RF waves do not interact with biological tissues and thus can penetrate deeper within the body than IR light.
Currently many research groups explore RF-activated AuNPs for cancer treatment, though there is no clear understanding what the exact mechanism of heat generation is. Some researchers presented evidences indicating that heat generation is a function of AuNPs size, another showed that it depends on ion concentration in the AuNPs colloidal suspension, others explain the phenomenon through the inductive, magnetic, or electrophoretic mechanisms.
In this study we investigated the energy absorption by AuNPs of different sizes, their supernatants, and different salts (AuNPs synthesis precursors) in the RF range 1-500 MHz. Our data indicates that in the colloidal AuNPs system supernatant accounts for most of the adsorption as compared to nanoparticles itself. In addition, effect of chemically vs. physically bound capping agent on absorption of AuNPs is also investigated. These findings provide an insight in the nature of RF-activated AuNPs colloids and considerations for RF-tumor ablation optimization.
10:30 AM - BM2.4.06
Spiky Gold Nanoparticles for Combinational Chemo-Immuno-Photothermal Cancer Therapy
Jutaek Nam 1 , James Moon 1
1 University of Michigan Ann Arbor United StatesShow Abstract
Spiky gold nanoparticles (SGNPs) have gained wide interest for biomedical applications as their surface plasmon resonance (SPR) can be tuned to the near-infrared (NIR) region depending on the dimensions of the “spiky” branches. However, SGNPs typically exhibit photothermal instability; SGNPs can transform into more stable spherical structures and hence lose SPR in the NIR region upon excitation due to heat-mediated melting and reshaping of “spiky” branches. Here, we addressed this challenge by applying mussel-inspired polydopamine (PDA) coating on SGNPs. We report that the PDA outer shell on SGNPs prevents photothermal reshaping of SGNPs and sustains their NIR-responsiveness. PDA coating can be achieved using spontaneous polymerization of dopamine under a mild basic condition in the presence of SGNPs. The PDA layer thickness can be controlled in a range of 1 – 30 nm by varying dopamine concentration. After NIR excitation, uncoated SGNPs undergo shape transformation to a more spherical form in a laser power dependent manner, whereas SGNP/PDAs maintain spiky branches and structural integrity. The transition to spherical shape for uncoated SGNPs is accompanied by progressive blueshifts in SPR absorption causing decreased efficiency of photothermal heating under prolonged laser irradiation. In contrast, SGNP/PDAs show minimum absorption shift in an identical condition resulting in significantly higher temperature increase compared with uncoated SGNPs. We further demonstrate multiple combinational tumor therapeutic approach by co-administrating Doxorubucin (Dox) with SGNP/PDAs for chemo-immuno-photothermal therapy. The SGNP/PDA-mediated photothermal treatment effectively eliminates bulk tumor burden and Dox-mediated chemo-immunotherapy prevents relapse of treated tumors. In addition, the combination generates potent anti-tumor memory immune responses that decreases growth of metastatic tumors and confer protection against tumor re-challenge. Immuno-modulations in response to the treatments are analyzed by the population of immune cells in tumor microenvironment. We also discuss the mechanism of immune response based on the antibody-mediated depletion study. In conclusion, PDA coating is a simple and versatile method to produce stable NIR-responsive gold nanoparticles, and the combinational chemo-immuno-photothermal therapy using PDA-coated SGNPs and Dox permits efficient tumor treatment promising a new form of cancer therapy.
10:45 AM - BM2.4.07
Intrinsically Theranostic Nanoparticle Derived from Dunellia for Phototherapy and Tissue Imaging
Dipanjan Pan 1 2 , Fatemeh Ostadhossein 1 , Santosh Misra 1 , Aaron Schwartz Duval 1
1 Department of Bioengineering University of Illinois at Urbana-Champaign Urbana United States, 2 Departments of Bioengineering and Materials Science and Engineering Carle Foundation Hospital Urbana United StatesShow Abstract
The problems arising from melanoma of skin has become a major public health issue in several countries. In the United States alone, it is estimated that 76,380 new cases will be diagnosed in 2016. Therefore, it is of prime importance to develop strategies to address this global issue. Herein, using a facile method, novel intrinsically therapeutic carbon nanoparticles (CNPs) are developed from Dunaliella Salina, a green microalgae bearing a high content of carotenoids. Carotenoid are terpenoid-based antioxidants with unique optical absorptive properties and benefit from preferential uptake by the cellular membrane due to their ability to be deeply fused with the lipid hydrophobic center. The water dispersible uniformly sized nanoparticles (2.6±0.5 nm) are derived through the hydrothermal synthetic approach and are extensively characterized for their chemical and physical properties. Transmission electron microscopy (TEM) and Atomic Force Microscopy (AFM) were utilized to observe the morphology of the CNPs. Subsequently, FT- IR spectroscopy revealed the presence of multiple hydrophilic surface moieties while Raman spectroscopy indicated the existence of well- established D and G bands of CNPs. Interestingly, although UV-Vis spectroscopy masked the contribution from carotenoid in the visible range (~530 nm), 1H NMR spectroscopy properly confirmed the intact nature of carotenoid after transformation to nanoparticles, suggesting that these CNPs are ‘enclosing’ carotenoid molecules. Hence, it was hypothesized that CNPs could be efficiently utilized as nanoparticles with ‘embedded cargo’ for melanoma eradication under UV absorption. MTT assay in malignant human melanoma cell line demonstrated that the reactive oxygen species could be induced after 30 minutes UV exposure (wavelength=362 nm) leading to a decrease in cell viability compared to untreated control, agave based CNPs and free β- carotene. In addition, Fluorometric Intracellular ROS Kit was applied to indicate the generated ROS concentration over the period of 48 h. Inspection of the results revealed the enhanced amount of species in algal CNPs compared to control and agave based CNPs. Furthermore, the localization of the nanoparticles and their chemical features are made feasible using Raman imaging in C32 cells incubated with nanoparticles. Overall, these inexpensive naturally derived multifunctional nanoplatforms hold promise as the next generation phototherapeutic agents with intrinsic efficacy in cancer eradication.
11:45 AM - BM2.4.09
Golden Nanoflowers for Image-Guided Radiotherapy
Gloria Jimenez Sanchez 1 , Nasser Mohamed Said 1 , Jeanne Volatron 2 , Iris Marangon 2 , Sandrine Dufort 3 , Geraldine Le Duc 4 , Rana Bazzi 1 , Florence Gazeau 2 , Stephane Roux 1
1 UTINAM Université de Bourgogne Franche-Comté Besançon France, 2 Université Paris Diderot Paris France, 3 Nano-H S.A.S. Saint Quentin Fallavier France, 4 ESRF Grenoble FranceShow Abstract
Owing to their large range of properties which can be accurately tuned by the chemical composition, the shape and the dimensions, multifunctional nanoparticles appear as promising candidates for image-guided therapy.
In this context, we developed the synthesis of gadolinium chelate coated gold nanoparticles (Au@L-Gd with L a linear or macrocyclic polyaminocarboxylate chelator) which are designed for combining radiotherapy and multimodal imaging (magnetic resonance imaging (MRI), scintigraphy (SPECT after radiolabeling by indium-111) and X-ray imaging) [1-5]. The presence of gold element confers to the nanoparticles a radiosensitizing effect which led to a great increase in lifespan (ILS) of brain tumor bearing rats when they were treated by radiotherapy after intravenous injection of the gold nanoparticles. However the radiosensitizing effect appears to be underexploited owing to a too rapid renal clearance which limits their accumulation in solid tumor. Hence the exploitation of the potential of these gold nanoparticles for MRI guided radiotherapy requires the increase of the circulation time for reaching efficiently their specific target while preserving the ability for renal clearance.
For achieving an enhanced circulation time of the gold nanoparticles and therefore a greater accumulation in solid tumor, Au@L-Gd nanoparticles were immobilized onto large bioresorbable carriers (maghemite nanoflowers (nF)) [6-8]. The resulting golden nanoflowers are constituted of monocrystalline grains (11 nm) which are assembled in a flower-shaped structure and gold nanoparticles (Au@L-Gd). Such an association allows combining the imaging modalities and therapeutic activities of each part of the golden nanoflowers (T1-weighted MRI, radiosensitization from the gold nanoparticles and T2-weighted MRI, magnetic hyperthermia from iron oxide nanoflowers). In comparison to the case of Au@L-Gd nanoparticles, the circulation of golden nanoflowers after intravenous injection is longer-lasting: the presence of the golden nanoflower is observed 1 h after the injection whereas the content of gold nanoparticles is too low in the tumor for monitoring their accumulation by MRI 1h after the injection. This was mainly attributed to the larger size of the golden nanoflowers (30 nm vs 2.5 nm). Moreover the radiosensitizing effect of the golden nanoflowers provides for a same gold content in the injected suspension a higher ILS than in the case of Au@L-Gd. The immobilization of the gold nanoparticles Au@L-Gd onto nanoflowers allows therefore to better exploit the radiosensitizing effect of the gold nanoparticles.
 Alric et al., J. Am. Chem. Soc. 2008, 130, 5908
 Arifin et al., Radiology 2011, 260, 790
 Alric et al., Nanoscale 2013, 5, 5930
 Miladi et al., Small 2014, 10, 1116
 Laurent et al., Nanoscale 2016, 8, 12054
 Hugounenq et al., J. Phys. Chem. C 2012, 116, 15702
 Lartigue et al., ACS Nano 2012, 6, 10935
 Javed et al., Small 2014, 10, 3325
12:00 PM - BM2.4.10
Electrodeposited Fe and Fe-Au Nanowires as MRI Contrast Agents
Daniel Shore 1 , Sylvie Pailloux 1 , Jinjin Zhang 1 , Michael Garwood 1 , Valerie Pierre 1 , Bethanie Stadler 1
1 University of Minnesota Minneapolis United StatesShow Abstract
Fe and Fe-Au nanowires were synthesized by electrochemical deposition for use as contrast agents in magnetic resonance imaging (MRI). Contrast agents are often used in MRI to distinguish different tissues and help make diagnoses. The size, shape, surface, and magnetic moment of these agents each affect performance in T1 or T2 contrast. Here, Fe and Fe-Au nanowires of various lengths (0.5-2.7μm), diameters (32-110nm) were made from single electrolytes. Au was added to some electrolytes to make nanowires. The Au segments were used for thiol-functionalization and may be useful for future photo-thermal therapy, biomolecular targeting, and drug delivery. The nanowires are also useful for magnetic hyperthermia because of their high magnetic moments and anisotropies. In this work, these promising multifunctional electrodeposited Fe and Fe-Au nanowires were found to be comparable to commercial T1 and T2 contrast agents with r1 = 2.0 mM-1s-1 and r2 = 77 mM-1s-1. Values of r1 were increased by increasing nanowire diameter, while r2 values were increased by decreasing nanowires lengths. Gold-rich segments were coated with SH-PEG-COOH, which increased the r2 by ~10X. Successful concentration-dependent contrast was seen in T2-weighted images, which proves the feasibility of these multifunctional nanowires as active MRI contrast agents.
12:15 PM - BM2.4.11
Characterization of Fullerenes Aggregates at Environmental Concentrations Using Laser Induced Breakdown Detection
Zelie Venel 2 , Julien Gigault 1
2 Cordouan Technologies Pessac France, 1 Environnements et Paléo-Environnements Océaniques et Continentaux, French National Center of Scientific Research Université de Bordeaux Talence FranceShow Abstract
The aim of our work is to develop unprecedented methods to measure ultra-trace concentration of engineered nanoparticles in aqueous and environmental solution. Currently, nanoparticles release is a worrying environmental issue to consider, due to the lack of knowledge concerning their behavior and fate. This lack is clearly due to the urgent need to have an accurate method able to characterize the several physical and chemical parameters of nanomaterials (size, size distribution, shape, charge, etc.) within the context of ultra-diluted sample in natural media. From all the analytical techniques generally used to characterize nanomaterials such as light scattering, electronic microscopy, optical spectroscopy, chromatographic methods, none of them can access directly to the nanomaterial (NM) characterization in natural media at ultra-trace concentration. In our study, we present for the first time the potentiality of the Laser-induced breakdown detection technology for the characterization of nanoparticles in aqueous media for environmental application. The calibration of this tool was first optimized using polystyrenes nanospheres at different environmentally relevant concentrations. The aim of this optimization part is to carefully check all the
instrumental details from the quality of the measurement cell to the development of measurement protocol in order to get an accurate and relevant statistical distribution. Then, we applied and validated our methodology on fullerene nanoparticles in aqueous media using different preparation pathways. The preparation methods are developed in order to simulate both environmental and biological conditions using mechanical agitation and additives such as polyethylene glycol based molecules. Our first results show for the first time the ability to differentiate size population of nC60 at low concentrations according to their structures and dispersion state.
12:30 PM - *BM2.4.12
Mechanism for the Cellular Uptake of Targeted Gold Nanorods of Defined Aspect Ratios
Hongrong Yang 1 , Chung Hang Choi 1
1 Chinese University of Hong Kong Shatin Hong KongShow Abstract
Biomedical applications of non-spherical nanoparticles such as photothermal therapy and molecular imaging require their efficient intracellular delivery, yet reported details on their interactions with the cell remain inconsistent. Here, the effects of nanoparticle geometry and receptor targeting on the cellular uptake and intracellular trafficking are systematically explored by using C166 (mouse endothelial) cells and gold nanoparticles of four different aspect ratios (ARs) from 1 to 7. When coated with poly(ethylene glycol) strands, the cellular uptake of untargeted nanoparticles monotically decreases with AR. Next, gold nanoparticles are functionalized with DNA oligonucleotides to target Class A scavenger receptors expressed by C166 cells. Intriguingly, cellular uptake is maximized at a particular AR: shorter nanorods (AR=2) enter C166 cells more than nanospheres (AR=1) and longer nanorods (AR=4 or AR=7). Strikingly, long targeted nanorods align to the cell membrane in a near-parallel manner followed by rotating by ~90° to enter the cell via a caveolae-mediated pathway. Upon cellular entry, targeted nanorods of all ARs predominantly traffic to the late endosome without progressing to the lysosome. Our studies yield important materials design rules for drug delivery carriers based on targeted, anisotropic nanoparticles.
BM2.5: Polymer-Based Systems I
Chung Hang Choi
Tuesday PM, November 29, 2016
Hynes, Level 1, Room 103
3:00 PM - BM2.5.02
Using Stop Flow Lithography to Synthesize Multi-Stimuli Responsive Drug Carriers#xD;
for Precisely Controlled Drug Release
Hyeon Ung Kim 1 , Dae Gun Choi 2 , Min Suk Shim 2 , Ki Wan Bong 1
1 Chemical and Biological Engineering Korea University Seoul Korea (the Republic of), 2 Division of Bioengineering Incheon National University Incheon Korea (the Republic of)Show Abstract
Stimuli-responsive drug carriers have been intensively researched for controlled drug release because they can alter their physicochemical properties in response to specific cellular stimuli. For effective cancer therapy, it is desirable to use multi-stimuli responsive drug carriers because cancer exhibits various levels of stimuli at different tumor sites and tumor progression stages. Multi-stimuli-responsive drug carriers are usually fabricated by emulsion method, droplet-based microfluidics, replication method, etc. Unfortunately, however, current methodologies have limitations to synthesize drug carriers which can independently respond to each cellular stimulus and then release suitable drugs in a controlled manner. For example, the synthesized drug carriers using these methods exhibit a burst drug release at complex stimuli without showing a controlled and sequential drug release responding to an each independent stimulus.[2,3]
Here, we introduce multi-sensitive drug carriers synthesized by stop flow lithography (SFL). The SFL is a promising platform to synthesize microparticles with complex geometries and chemical patterns. Using this platform, we synthesized multi-compartmental drug carriers with chemically distinct compartments composed of different stimuli-responsive polymers. Each compartment of the drug carriers was synthesized with reducible disulfide-containing crosslinkers and acid-cleavable ketal-containing crosslinkers to selective release the independent drug in response to tumor miroenvironments (i.e., highly reductive and mildly acidic conditions). We successfully fabricated multi-compartmental particles where each compartment of the drug carriers encapsulates multiple drugs individually. The particles exhibited independently controlled drug release at different stimuli. We believe that multi-stimuli responsive drug carriers can be utilized for efficient treatment of tumor with heterogeneous tumor microenvironments.
 Wang, Jinqiang, et al. Advanced Materials 2013, 3670.
 Wu, Yanjuan, et al. RSC Advances 2015, 31972.
 Chen, Xin, and Zhongning Liu. Journal of Materials Chemistry B 2016, doi:10.1039/C6TB00694A.
 Hwang, Dae Kun, et al. Journal of the American Chemical Society 2009, 4499.
3:15 PM - BM2.5.03
Photo-Responsive Acidifying Nanoparticle Restore Lysosomal pH and Cellular Function
Jialiu Zeng 1 , Kyle Trudeau 3 , Aaron Colby 1 , Orian Shirihai 2 3 , Mark Grinstaff 1
1 Department of Biomedical Engineering Boston University Boston United States, 3 Department of Medicine Boston University Boston United States, 2 Department of Medicine University of California, Los Angeles Los Angeles United StatesShow Abstract
We have developed a novel photo-responsive, acidifying nanoparticle (paNP) that acutely restore pH of compromised lysosomes to rescue autophagic flux and cellular function in beta cells and hepatocytes under lipotoxicity. In pancreatic beta-cells (INS1) and liver hepatocytes (HepG2), chronic exposure to high levels of fatty acids (lipotoxicity) leads to an inhibition of autophagic flux and subsequent cellular dysfunction, which has been recently associated with impaired lysosomal acidification and elevated lysosomal pH. Therefore, restoration of lysosomal pH is essential in alleviating the block in autophagy and promote proper cellular function. Currently, there is a lack of approach to deliver “acid” into a specific subcellular compartment at a desired time. To modulate lysosomal pH and determine its effect on autophagy in a time-dependent manner, we have designed a novel photo-activated acidic nanoparticle (paNPs) that contains caged acid which can be uncaged by acute photo (UV)-activation of the nitrophenylethanol protecting group. Rhodamine labelled paNPs demonstrate dose dependent uptake into lysosomes of INS1 and HepG2 cells. Acute photo activation of paNPs for 5 minutes in INS1 and HepG2 cells exposed to lipotoxicity demonstrate controlled acidification of lysosomes and restored lysosomal pH with minimal cell cytotoxicity. Photo-activated paNPs also increased lysosomal cathepsin enzyme activity, and decreased both autophagic proteins LC3II and p62 levels, indicating both a rescue of lysosomal function and autophagic flux due to restoration of lysosomal acidity. Additionally, paNPs restored glucose-stimulated insulin secretion that is reduced in INS1 cells and mouse islets under lipotoxicity. These results indicate that acidifying lysosomes with paNPs improved lysosomal function and autophagic flux in INS1 and HepG2 cells under lipotoxicity, and are of therapeutic interest for pathologies associated with lysosomal acidity impairment such as type II diabetes and non-alcoholic fatty liver disease (NAFLD).
3:30 PM - BM2.5.04
Near-Infrared Fluorescent Polymer Nanoparticles for Imaging Dopamine and Monitoring Neural Activity
Pei-Jian Feng 1 , Yu-Lei Chen 1 , Xuan-Zhong Xiao 1 , Cheng-Gen Qian 1 , Qun-Dong Shen 1
1 Nanjing University Nanjing ChinaShow Abstract
Brain imaging can measure the activity of large sets of neurons and analyze the brain circuits. The fluctuation of dopamine, an indispensable neurotransmitter, level in brain indicates a wide range of disease, including tumors of neural crest, drug addiction, and Parkinson disease. Particular interest focuses on dopaminergic tissue in different brain regions, and neural activity mapping is essential for early disease surveillance and therapy tracking. Near-infrared fluorescence (NIRF) imaging has been widely used to monitor therapy of cancer and other diseases in preclinical studies; however, this technology has not been applied smoothly to monitoring neural activity through dopamine. We design near-infrared fluorescence conjugated polymer with phenylboronic acid tags, which can self-assemble into biocompatible nanoparticles. Due to photo-induced charge transfer between the nanoparticles and the neurotransmitter, as well as optical signal amplification by molecular wire effect of the conjugated polymer, the nanoparticles can detect endogenous dopamine in living PC12 cells and variation in the neurotransmitter level distribution in mice brain.
3:45 PM - BM2.5.05
Bacteria-Responsive Hyaluronic Acid-Penicillin Conjugates as Highly Effective, Versatile Antibacterial Polymers
Nisha Hollingsworth 1 , Sarah Cowles 2 , Dahlia Alkekhia 2 , Noelly de Queiroz Ribeiro 3 , Rodnei Rossoni 3 , Beth Fuchs 3 , Anita Shukla 2
1 Macromolecular Science amp; Engineering, College of Engineering University of Michigan Ann Arbor United States, 2 School of Engineering Brown University Providence United States, 3 Division of Infectious Diseases Rhode Island Hospital Providence United StatesShow Abstract
The imminent threat of antibiotic resistance requires the development of new antibiotics to treat bacterial infections. We have repurposed existing penicillin antibiotics into polymer-penicillin conjugates, providing an effective method for the development of novel biocompatible antimicrobial polymers that exhibit enhanced activity in the presence of bacteria. Our novel conjugates display superior antibacterial efficacy compared to non-conjugated penicillins and prevent the attachment of bacteria.
We have used mild, aqueous colloidal carbodiimide chemistry (Manju 2011) to conjugate hyaluronic acid (HA) to common penicillin antibiotics via a labile ester bond sensitive to acidic pH, characteristic of infection. HA is degradable by hyaluronidase, an enzyme upregulated by common bacteria during infections (Ibberson 2014). Therefore, these HA-penicillin conjugates are bacteria-responsive, degrading in either acidic pH or hyaluronidase to form active penicillin-containing subunits. Our library of conjugates contains three narrow spectrum penicillins: carbenicillin, penicillin G, and ampicillin and two more recent penicillins effective against methicillin-resistant strains: nafcillin and oxacillin. FT-IR and size exclusion chromatography were used to confirm successful conjugation. The antibacterial efficacy of the products was examined using broth microdilution assays against gram-positive strains across a spectrum of penicillin resistance, including Staphylococcus aureus, methicillin-resistant S. aureus, and S. pyogenes, as well as gram-negative Pseudomonas aeruginosa. We determined that the conjugates were approximately 10 to 103 times more effective than the unconjugated penicillin controls. For example, HA-oxacillin conjugates were approximately 3500 times more effective than oxacillin alone against one particular strain of MRSA, USA300. Animal studies using an invertebrate model, Galleria mellonella, demonstrated the same enhanced efficacy of the conjugates in vivo. Additionally, these HA-penicillin conjugates were developed into micron-scale self-defensive antibacterial coatings, and were characterized by atomic force microscopy, profilometry, and scanning electron microscopy. Bacteria were unable to attach to the conjugate coated glass at a surface concentration of 0.32 μg/mm2, promising for preventing the development of biofilms. Finally, the conjugates were determined to be non-hemolytic at concentrations 103 times greater than what is needed to eradicate bacteria. Our conjugates prolong the lifetime of existing therapeutics by reducing the required dose of the therapeutic, and thus lowering susceptibility to resistance, while demonstrating potential to be used in both injectable and topical therapies.
4:30 PM - BM2.5.06
Distinct Increase on Stability Properties of Nanoparticles by Usage of Tailor-Made Polymer Micelles and Implementation of Innovative Encapsulation Strategies
Marcus Janschel 1 , Johannes Ostermann 2 , Jan-Philip Merkl 1 , Artur Feld 1 , Rieke Koll 1 , Horst Weller 1 2
1 Physical Chemistry University of Hamburg Hamburg Germany, 2 Centrum für Angewandte Nanotechnologie GmbH Hamburg Germany