Symposium SM8 : Bioinspired Metal Nanoparticles---Synthesis, Properties and Application

Inspired by nature, many peptide- and protein- based synthetic methods have been developed for the preparation of nanostructured inorganic materials. The unique integration of biomacromolecules and inorganic nanomaterials demonstrated excellent potentials in biological applications. However, despite the great success achieved so far, the fundamental understanding of interactions between biomolecules and materials remains elusive. To some extent, this is because the complicated folding of proteins and peptides make the prediction of peptide- and protein- functions too difficult. Furthermore, although peptides and proteins can provide improved solubility, biocompatibility and bio-targeting to inorganic nanomaterials, they are often problematic for biological applications because of their poor stabilities at nanoparticle surfaces and within living systems.

Peptoids, or called poly-N-substituted glycines, have advantages in that they are sequence-specific, biocompatible, and thermally, chemically and biologically stable. They can be cheaply and efficiently synthesized and several hundred commercially available amines can be used to build the large side-chain diversity. Libraries of peptoids have been demonstrated to be rich sources of protein-binding ligands and are non-immunogenic in mice. In contrast to proteins and peptides, they lack intra- and inter-molecular backbone hydrogen bonds and backbone chirality, but their large side-chain diversity makes them possible to attain sequence-specific molecular recognition for biological applications. Here we report the development of sequence-defined peptoids as a novel platform for controlled synthesis of hierarchical gold nanosuperstructures through peptoid engineering. By rationally varying the sidechain chemistry of peptoids, we generate a rule of designing peptoids that govern the morphological control of gold nanosuperstructures. For example, we found that the level of peptoid hydrophobicity and the presence of [N-(4-aminobutyl)glycine (Nab)] sidechains for binding affinity are critical for the flower-like gold nanosuperstructure formation. The mechanistic studies of peptoid-controlled formation of gold nanosuperstructures and their potentials as active SERS (surface enhanced Raman scattering) materials, will be also discussed.

Silver and gold nanoparticles are probably the most important types of metallic nanoparticles, due to their optical properties (gold), their antibacterial properties (silver), and the possibility for a surface functionalization with molecules by thiol-coupling chemistry. Chemical synthesis methods typically involve a reduction of the dissolved metal salts, e.g. by citrate, ethylene glycol or glucose, followed by the capping with suitable molecules or polymers. The control of their size and shape is of special importance for their physicochemical properties (like the plasmon resonance) and their biological effect (like the uptake into cells).
The fundamental processes that determine the biological action of silver nanoparticles will be demonstrated:
- Oxidative dissolution under the release of silver ions.
- Uptake into cells by endocytosis.
- Cytotoxic action of the released silver ions.
- Precipitation of the released silver ions as nanoscopic silver chloride.
- Influence of shape and size on the cytotoxicity.
This concept is extended to alloyed silver-gold nanoparticles. A synthetic pathway is presented which allows to control the particle size (typically 6 nm) and the silver-gold ratio in the full concentration range. In these, both optical and biological effects can be fine-tuned. For ultrasmall silver-gold nanoparticles (about 2 nm in diameter), autofluorescence is observed that can be used to track the pathway of the particles inside cells. On the other hand, larger metallic nanoparticles lead to an efficient quenching of attached fluorescent molecules.
The ultrastructural examination of alloyed silver-gold nanoparticles (6 nm) indicates that the particles are not a homogeneous alloy but possess a gold-rich core and a silver-rich shell which is the result of the simultaneous reduction of silver and gold salts: The more noble gold is reduced first.

Thermoplastics have revolutionized human life due to their ease of fabrication and low cost. A common and effective approach to mechanical enforcement of thermoplastics is inclusion of micro- or nanofillers of higher strength and elastic modulus. Conventionally, the fillers are dispersed by shear mixing in molten polymer, where viscosity of the mixture is dramatically increased due to large interface area. Accordingly, the dispersion is not efficient and filler content is typically limited to below 5% by weight.

The present work develops a novel technique for dispersing nanofillers in a thermoplastic polymer where polycondensation and dispersion of the nanofillers occur simultaneously via dynamic emulsion polycondensation at ambient temperature. The composite is manufactured in the form of a uniform powder, which can be molded into desired shape by melting. The technique is demonstrated for silver nanowire - Nylon 66 nanocomposites. In this demonstration, Ag nanowires are synthesized by polyol process. Polyvinylprrolidone (PVP) is used to functionalize the Ag nanowires. Composites with Ag weight fraction of 1.49%, 3.28%, 6.74% are prepared and characterized by SEM, TEM, UV-Vis, XRD, Raman scattering, FTIR, DSC and Nano-indentation.

The Ag nanowires are found to be monodispersed and hydrogen-bonded to the Nylon 66 matrix through PVP. Glass transition temperature of the composites decreases from 61 to 48 °C with Ag weight fraction increasing from 0 to 6.47%. The decrease of the glass transition temperature is owed to the plasticizer effect as well as heterogenous nucleation effect of the nanowires for polymerization leading to shorter chain length. Finally, mechanical properties of the composites show insignificant variation with the filler content. This absence of the composite effect is explained by Halpin-Tsai model, where the filler enforcement and decrease in matrix modulus counterbalance.

Viral templating is a promising method for nanobioconjugate synthesis at ambient conditions. With distinct morphology, modifiable molecular recognition, and low dispersity, viruses provide an excellent scaffold for a variety of metal nanostructures. However, due to structural restrictions associated with viral capsid assembly, large changes in viral shape are not typically well tolerated. As such, a new template must be selected for each desired metallic nanostructure geometry (i.e. spheres, rods, filaments). In this work, we have studied the transformation of a gold-binding M13 bacteriophage from filament to spheroid, as well as the effect of this shape change on templated gold synthesis. The gold-binding virus was previously genetically modified to display an 8-mer peptide with gold affinity on each of the pVIII major coat proteins found along its length. A simple chloroform treatment was used to cause a geometric conversion which resulted in a 13-fold contraction in phage length. The substantial reduction in template anisotropy resulted from significant rearrangement, and likely disordering, of the major coat proteins. The gold synthesis capabilities of the transformed viral templates were investigated using chloroauric acid as a source of gold ions and sodium borohydride as a reducing agent. Transmission electron microscopy was used to compare the size, shape, and morphology of the gold synthesis products prepared using filament- and spheroid-shaped M13 templates. It was found that not only was the long range geometry modified, but the size and shape of the grains of the synthesized gold were unique to the template. Using the same synthesis conditions, the filamentous form of the gold-binding phage produced discrete (non-coalesced) isotropic particles approximately 6 nm in diameter whereas the spheroidal form yielded coalesced, plate-like structures more than 100 nm in size. Zeta potential was measured to better understand the interaction of gold ions with both template geometries. In addition, absorption measurements were used to evaluate the optical performance and surface plasmon resonance of the templated gold nanomaterials. Here, we have investigated the conversion of the filamentous M13 phage to a spheroids, and demonstrated that the morphological and optical properties of viral-templated Au synthesis products were greatly influenced by the arrangement of both the capsid proteins and the affinity peptides. Shape transformation of viral-templates, such as the M13, represents a new and important route to geometrically-tunable hierarchical metal-based nanobioconjugates.

Gold nanowires supported on a polymer anion exchange resin were prepared using solution-phase techniques, which yielded a topology that is analogous to a sea urchin. The resulting anisotropic gold nanostructures are of interest for a range of applications that include catalysis, electrochemical sensing, and photothermal based materials due to the high aspect ratios, and good thermal and electrical conductivity of these products. Growth of gold nanowires in solution using structure-directing surfactants tends to produce relatively low aspect ratio materials or to have relatively low yields and structure uniformity for high aspect ratio materials. In contrast, growth of gold nanowires mediated by the surfaces of the polymer resin is able to overcome these deficiencies. In the study presented here, gold nanowires were synthesized by a modified hydrothermal method that utilized polymer ion exchange resins to mediate the growth of the nanowires. The aspect ratios, structural purity and yield of gold nanowires are studied as a function of the reaction conditions and chemical species in the growth solution, such as the concentration of disodium ethylenediaminetetraacetate, cross-linking density and ion exchange capacity of the polymer resin, and reaction temperature. These studies provide a new insight into the mechanism of growth of these gold nanowires. In addition, a unique sea urchin-like topology was achieved that is different from previous reports in the literature for polymer mediated preparation of gold nanowires. The results of this study provide insight into preparing gold nanowires with other topologies and for a variety of applications that include their use as materials in stretchable and/or flexible electronics.

Gold nanostructures have attracted extensive research interest in their biomedical applications due to their tunable optical properties and good biocompatibility. Particularly, their tunable plasmonic properties give rise to strong and tunable optical absorption properties, and therefore, hold great promises for photothermal therapy. To date, a number of different gold nanostructures, including aggregated nanoparticles, nanoshells, nanorods, and nanocages, have shown great near infrared (NIR) absorption and served as photothermal therapeutic agents. One of the immediate challenges remaining in this field is how to control the size of these nanostructures to be small enough for effective delivery to target cells while maintaining strong and tunable NIR properties. We recently have developed adaptive ionic layer epitaxy (AILE) that employs ionic surfactant monolayers to produce 2D non-van de Waals solid metal oxide nanosheets with few-nanometer thickness. In AILE, an ionic surfactant monolayer is first formed at the water-air interface, under which the aqueous solution contains precursors for the desired materials. Due to the specific bonding between ionic surfactant head groups and the aqueous precursor ions containing the opposite electric charge, the intermolecular spacings between the ionic surfactant at the monolayer can adapt to the lattice spacings of the grown material and guided the 2-D growth of nanosheets. With AILE, we have now been able to prepare 4-nm thick Au nanosheets. Transmission electron microscopy (TEM) was used to monitor the evolution of the Au nanosheets and determined their nanocrystalilne nature. UV-Visible spectroscopy shows that they have a broad and strong absorption in the NIR region. Surfactant molecules with different head groups were selected to form monolayers at the water-air interface to guide the formation of Au nanosheets. By controlling the experimental conditions, we are also able to tune the thickness and grain size of the Au nanosheets. The lateral size of the nanosheets can be broken down from tens of microns to tens of nanometers by high-power sonication. The capability of controlling the dimensions and the polycrystalline structures of the nanosheets allows us to tune their NIR absorption properties. The Au nanosheets were tested as photothermal therapeutic agents against 4T1 murine breast cancer cells.

Synthesis of silver and zinc oxide nanoparticles was the focus of this work because of their wide range of applications in the field of medicine for use as antibiotics, for food preservation and in agriculture. The nanoparticles were synthesized using Ocimum gratissimum and Vernonia amygdalina leaf extracts. The resulting nanostructures were studied using Scanning and Transmission electron microscopy, X-ray diffraction and optical spectroscopy. Biosynthesis of nanoparticles preferred to chemical and physical methods is cost effective, eco-friendly and gives nanoparticles which are stable over fairly long periods of time. Biosynthesis rely on biomolecules such as phenols, flavonoids, proteins, alkaloids, steroids, carbohydrates and glycosides to act as reducing and stabilizing agents and sometimes provide capping effect discouraging the nanoparticles from agglomerating. It was found that varying the concentration of the leaf extract or precursor materials changed the physical and optical characteristics of the resulting nanoparticles and some applications in agriculture and for food preservation are being investigated. Cyclic voltammetry was also used to study the electrodeposition of silver metal on gold and carbon coated electrodes.

Silk fibroin has been recognized as a powerful protein biomaterial owing to its unique combination of mechanical properties, biocompatibility, slow degradability, versatility in processing and ability to be interfaced with inorganic materials. Here, we introduce a design for biocompatible multifunctionalized silk microcontainers that can be utilized for targeted delivery and release of encapsulated cargo. Robust microcapsules were prepared from regenerated silk fibroin by locking in β sheets in silk secondary structures during Layer-by-Layer assembly on sacrificial spherical templates. Entrapment of the cargo within the capsule walls was demonstrated with fluorescent dyes. Functionalization of silk fibroin microcapsules with gold nanoparticles (AuNPs) was achieved during in situ reduction of chloroaurate anions. As opposed to electrostatic adsorption of NPs within the counter-ion layers, reduction of Au on the surface of themicrocapsule shell allowed further biofunctionalization of NPs with antibodies. By adjusting the reducing conditions (choice of the buffer, reaction temperature, concentration of chloroauric acid), a narrow distribution of size and shape of AuNPs can be attained to achieve the proper conjugation of the antibodies to metal surfaces. Additionally, as the result of incubation in the reducing buffer solutions, further reinforcement of silk microcapsules was observed by increasing intra and intermolecular hydrogen bonding and hydrophobic interactions during oxidation of amino acids. Future plans will be focused on targeted delivery of the silk microcapsules to recombinant bacterial cells via specific antibody-antigen interactions and unloading of the entrapped cargo upon irradiation with short laser pulses in the near-infrared wavelength. The design of targeted delivery using biocompatible multifunctional silk microcapsules has a number of potential applications, including in vivo delivery, bio diagnostics and biotherapy.

An increasing need for novel and cost-effective fabrication of one dimensional (1-D) nanostructures for electronic and optoelectronic applications has fostered interest in bio-assisted assembly techniques. Unlike many conventional nanofabrication approaches, biomolecules offer unparalleled specificity and nanoscale precision under ambient, environmentally-friendly conditions. A broad selection of biomolecular templates are available, ranging from proteins to DNA to viruses. One bacteriophage which has proven its versatility in bio-assisted assembly is the M13 filamentous virus. This high-aspect-ratio phage has been used to assemble a variety of nanomaterials and devices. In this research, we have utilized the M13 bacteriophage as a 1-D scaffold for gold/polypyrrole (Au/PPy) nanopeapod fabrication. A genetically-modified, Au-binding phage was used to template linear chains of Au NPs which were subsequently coated with PPy using electropolymerization. The electrodeposition potential and time of the conductive polymer layer were varied resulting in a range of morphologies from a thin (~8-18 nm) conformal shell to a thick continuous film with microscale features. Using two-terminal room-temperature measurements, the electrical behavior and real-time chemiresistive sensing response of these viral-templated structures were characterized before and after electrodeposition. Au/PPy nanopeapod-based devices displayed an average ammonia (NH₃) sensitivity of 0.3%/ppm for gas concentrations ≤ 10 ppm and a calculated lowest detection limit (LDL) of 0.007 ppm. A post-deposition acid treatment was used to modify the electrical behavior of the hybrid materials through overoxidation of the PPy shell. The increased Debye length within the PPy layer enhanced the measured NH₃ sensitivity to 1.26%/ppm while maintaining a low calculated LDL of 0.005 ppm, which is comparable or better than many reports based on high-aspect ratio PPy nanomaterials. The enhanced sensing performance was attributed to the extremely thin conductive polymer layer enabled by viral-assisted assembly, in addition to catalytic effects associated with the Au NPs.

Since many years, gold nanoparticles (NPs) have attracted attention for their remarkable properties, especially in plasmonics. Their syntheses are generally based on the reduction of gold(I) or (III) compounds in the presence of molecules that can bind to the surface of NPs and protect them against aggregation. Common capping ligands are thiols or phosphines. Much less common, yet promising, ones are N-heterocyclic carbenes (NHC),¹ which were recently shown to be more stable ligands than thiols in self assembled monolayers.² This higher binding affinity, which involves an Au-C bond, could be very interesting for applications where the ligands should not be released, such a those related to nanomedecine.
A two steps synthesis of NHC protected gold NPs was reported in 2013.³ It involved a N,N'-bisalkylimidazolium tetrachloroaurate as precursor, which is first treated with sodium hydride to deprotonate the imidazolium ring and generate in situ the NHC. Then, gold(III) reduction is performed with sodium borohydride and monodispersed gold NPs around 5 nm are obtained.
We have found that the first step involving sodium hydride could be skipped. Indeed, treating directly N,N'-bisalkylimidazolium tetrachloroaurate with sodium borohydride results also in the formation of gold NPs. To clarify the nature of the capping ligands in this direct synthesis and their interactions with the gold surface, analysis by XPS and NMR have been conducted. Moreover, to increase the ligand to gold ratio, which is a common way to controlled the size of NPs, syntheses in which various amounts of N,N'-bisalkylimidazolium halide have been added, were also performed.


1. A.V. Zhukhovitskiy, M.J. MacLeod, J.A. Johnson Chem. Rev. 2015 (doi:10.1021/acs.chemrev.5b00220).
2. M.C. Crudden, J.H. Horton, I.I. Ebralidze, O.V. Zenkina, A.B. McLean, B. Drevniok, Z. She, H.B. Kraatz, N.J. Mosey, T. Seki, E.C. Keske, J.D. Leake, A. Rousina-Webb, G.Wu Nat. Chem. 2014, 6, 409-414.
3. C.J. Serpell, J. Cookson, A.L. Thompson, C.M. Brown, P.D. Beer Dalton Trans 2013, 42, 1385-1393.

Gold nanoparticles (AuNP) have been widely used in various biomedical applications due to its biocompatibility, simple synthesis, facile surface modification, versatile conjugation with biomolecules, and tunable optical properties. Moreover, AuNPs have been known to have an anti-angiogenic effect by binding vascular endothelial growth factor (VEGF) which plays a crucial role in the pathogenesis of rheumatoid arthritis (RA). In this work, hyaluronate - gold nanoparticle / Tocilizumab (HA-AuNP/TCZ) complex was prepared for the treatment of RA. TCZ is a humanized monoclonal antibody against the interleukin-6 (IL-6) receptor and used as an immunosuppressive drug by interfering IL-6 in the pathogenesis of RA. HA is known to have cartilage-protective and lubricant effects and can be used as stabilizer of AuNPs. HA was modified with cystamine via reductive amination, which was reduced with dithiothreitol (DTT) to prepare end-group thiolated HA (HA-SH). AuNP was chemically modified with HA-SH and physically modified with TCZ. The formation of HA-AuNP/TCZ complex was corroborated by UV-Vis spectroscopy, dynamic light scattering (DLS), and transmission electron microscopy (TEM). The therapeutic effect of HA-AuNP/TCZ complex on RA was confirmed in collagen induced arthritis (CIA) model mice by ELISA, histological, and western blot analyses. Taken together, we could confirm the feasibility of HA-AuNP/TCZ complex as a dual targeting drug candidate to VEGF and IL-6R for the treatment of RA.

Ag-Graphene nanocomposite solution exhibits strong antibacterial activity against both Gram Positive and Gram Negative bacteria. The antibacterial property of this nanocomposite was previously tested by Kirby-Bauer assay disk diffusion and Minimum Inhibitory Concentration (MIC) assay using P. aeruginosa and S. aureus as model strains for both types of bacteria. We hypothesize that by applying an external electric bias(Electroporation); a decrease in the bacterial inhibition time (less than 6 hrs) can be attained. Preliminary data indicate that there is a significant difference in bacterial growth between the control and experimental groups treated with electroporation. We are performing a systematic study with different types of bacteria, at various concentrations of Ag-Graphene nanocomposite, and different levels of exposure to electroporation. Through this study we will determine the optimum parameters (nanocomposite concentration and electroporation time) that facilitate the internalization of Ag-Graphene nanocomposite into the bacteria and enhance the corresponding bactericidal effects. We will also discuss the mechanism(s) for the incorporation of the nanoparticles and the subsequent damage to the bacteria. Taking advantage of the high biocompatibility of graphene and the antibacterial activity of silver, the Ag-GQD nanocomposite becomes an effective nontoxic biomaterial suitable for numerous applications, such as self-sterile textiles, biomedical devices, coatings, and cosmetics.

Over the past decades, nanoparticles (NPs) have emerged as a new class of therapeutics to improve actual cancer therapies, often inadequate and lacking of specific action. A wide range of nanomedicine is currently under investigation. Among them, gold nanoparticles (AuNPs) are considered one of the most promising nanocarriers thanks to their unique optical properties which make them ideal theranostic agents combining drug delivery, photothermal therapy and imaging. Furthermore their reactive surfaces render them highly tunable with drug loading and active targeting abilities. Although nanomaterials are usually able to successfully enter cells by endocytosis, the subsequent trafficking to the cytoplasm is generally hindered by the degradation in lysosomes. Synthetic polymers have been designed to mimic the role of the fusogenic viral peptides such as PP75 (75mol% of _L-phenylalanine grafted on poly(_L-lysine iso-phtalamide)) which demonstrated high membrane disruptive ability at endosomal pH and successful cytoplasmic delivery of drugs in vitro and in vivo. Herein, we report the preparation of a novel type of nanocarrier combining the advantages of AuNPs with the endosomolytic properties of the anionic amphiphilic PP75. To our knowledge this is the first time such hybrid NPs are reported. The NPs exhibited excellent colloidal stability in buffer at physiological pH but upon pH decrease to pH 5, they agglomerated quickly due to the hydrophobic associations of PP75 layer as observed with the change of the hydrodynamic size, zeta potential and surface plasmon resonance properties. We also demonstrated a fast and almost complete reversibility of the process for a series of cycles. This may constitute a real asset for drug delivery increasing the local concentration around the tumour site which exhibits slightly more acidic pH than healthy cells, and leading to: (i) enhanced drug concentration; (ii) more heat generated during phototherapy and (iii) enhanced contrast for imaging. The reversibility is also fundamental to avoid the permanent aggregation of NPs in the body. In addition in vitro results showed a successful delivery of model drugs into the cytoplasm of HeLa cells after endosomal release and a low non-specific cytotoxicity effect after 24h incubation and up to 10nM NPs. Further studies showed that the membrane activity of the nanocarrier could be enhanced using poly(ethylene glycol) as a spacer, with significant increase of the model drug released from liposomes used as model drug of the endosomal membrane. These results demonstrated the potential viability of such hybrid NPs as drug nanocarriers and cytoplasmic delivery systems. We strongly believe that this study provides new insights for the development of responsive drug delivery platforms in nano-oncology.

Metal alkoxides are widely used in the ceramics and sol-gel manufacturing, but their use with organic molecules has been limited due to their highly reactive nature. Thus far the reactions of metal alkoxides and bioorganics have been conducted either in vacuum with CVD technology¹ or with rigid templating.² We have proven that the reaction between iron (III) isopropoxide and lignin³ in THF solution produces a variety of morphologies, ranging from uniform nanospheres to nanofishnets and hollow nanospheres. The resulting structure can be controlled by varying the parameters of the immediate condensation reaction between lignin and iron isopropoxide. Despite iron isopropoxide being highly water sensitive, the formed structures are stable as water suspensions. The formed particles are paramagnetic or superparamagnetic depending on the obtained domain size. Our results demonstrate that solution processable bioorganometallic structures can be easily produced with macromolecular polyols in an inert solvent, such as THF. This presents a facile method for obtaining a wide range of organometallic materials, with a large variety of metal alkoxides and organic polyols to choose from. We anticipate that bioorganometallic sol-gel reactions will produce biocompatible materials with enhanced functionality, such as magnetic, antibacterial and catalytic properties.

(1) Korhonen, J. T.; Hiekkataipale, P.; Malm, J.; Karppinen, M.; Ikkala, O.; Ras, R. H. a. Inorganic Hollow Nanotube Aerogels by Atomic Layer Deposition onto Native Nanocellulose Templates. ACS Nano 2011, 5, 1967–1974.
(2) Andre, R.; Tahir, M. N.; Natalio, F.; Tremel, W. Bioinspired Synthesis of Multifunctional Inorganic and Bio-Organic Hybrid Materials. FEBS J. 2012, 279, 1737–1749.
(3) Lievonen, M.; Valle-Delgado, J. J.; Mattinen, M.-L.; Hult, E.-L.; Lintinen, K.; Kostiainen, M. a.; Paananen, A.; Szilvay, G. R.; Setälä, H.; Österberg, M. Simple Process for Lignin Nanoparticle Preparation. Green Chem. 2015.

Nanocomposite materials with multifunctional abilities are giving rise to a conceptually innovative set of devices, implants and theranostic agents which are a new generation of biomedical applications. The most basic approach is to combine in a single core@shell platform with substantially different functionalities arising at the nanoscale, like superparamagnetic (SPM) behavior or localized surface plasmon resonance (LSPR), [1] by properly selecting the type of material (metals, oxides@metals, etc). However, complex fields, like tissue engineering, require sophisticated nanocomposite materials with specific biocompatible, textural and mechanic features allowing the proliferation and dynamic regeneration of cells, fibers and vascularization.
A new approach based on magnetic scaffolds can be afforded by doping with Iron or magnetic Iron-Oxide NPs biocompatible matrices [2] (hydroxyapatite (HA), polycaprolactone (PCL), chitosan, collagen, or mesoporous silica SBA-15) which combine porosity, mechanical strength, SPM behavior and/or LSPR response [3] which endow the final material for: magnetic guiding of nanocarriers; magnetic hyperthermia (MH) treatment[4], drug delivery, magnetic resonance and/or plasmonic imaging, magnetic cell stimulation or magnetic fixation.
In this talk, experimental details about the preparation, magnetic hyperthermia of different SPM core@shell NPs ( Fe@Au; Fe₃O₄; Fe₃O₄@Au), metal Atomic Quantum Clusters (AQCs) and magnetically doped biocompatible scaffold formulations based on HA, chitosan, PCL or mesoporous SBA-15 silica, will be shown.

[1] Y. Piñeiro, Z. Vargas, J. Rivas, M. Arturo López-Quintela. EurJICS, Iron Oxide based Nanoparticles for Magnetic Hyperthermia Strategies in Biological Applications.4495-4509, (2015).
[2] M. Bañobre-López, Y. Piñeiro-Redondo, M. Sandri, A. Tampieri, R. De Santis, V. A. Dediu and J. Rivas. Hyperthermia Induced in Magnetic Scaffolds for Bone Tissue Engineering. IEEE Trans. on Magn., 50, 5400507(1-7),( 2014).
[3] J. Rivas, Y. Piñeiro, E. Iglesias-Silva, J. M. Vilas-Vilela, L. M. León, A. López-Quintela,
Air-stable Fe@Au nanoparticles synthesized by the microemulsion’s methods
J. Korean Phys. Soc, vol. 62, n.10, pp.1372-1381, (2013).
[4]J. Rivas, M. Bañobre-López, Y. Piñeiro-Redondo, B. Rivas, M.A. López-Quintela. Magnetic nanoparticles for application in cancer therapy. Journal of Magnetism and Magnetic Materials 324, 3499–3502, (2012)

Recent years have seen heightened applications of magnetic nanoparticles (NPs) for cancer therapeutics and diagnostics. Most of these involve superparamagnetic iron oxide NPs (SPIONs), in which the particles behave as paramagnets with a huge magnetic moment.1-4
In this talk I will briefly summarize progress in these areas and discuss two avenues recently explored. The first involves the efficient one-step synthesis and detailed physico-chemical evaluation of SPIONs carrying the anticancer drug doxorubicin (DOX) and coated with the covalently bonded biocompatible polymer poly-(ethylene glycol) (PEG), either native or modified with the biological cancer-targeting ligand folic acid (PEG-FA). An alternative approach consists of drug loading and release from SPIONs dispersed in thermosensitive gel emulsions with external triggering by an alternating magnetic field for use in on-demand drug delivery implants.
Finally, I will present recent work using synchrotron x-ray techniques (SAXS, XANES and XPS) to obtain a detailed characterization of SPIONS used in biomedical applications.
*Work performed in collaboration with I. Milosevic and L. Motte (University of Paris 13), M. Tadic (University of Belgrade), E. Allard-Vannier, I. Chourpa and K. Kaaki (University of Tours), H. Khurshid and H. Srikanth (University of South Florida) and B. Aoun, T. Li, Y. Ren and C.-J. Sun (Argonne National Laboratory).
References 1) K. Hervé et al., Nanotechnology 19, 465608 (2008). 2) K. Kaaki et al., Langmuir 28, 1496 (2012). 3) J. Gautier et al., Int. J. Pharm. 423, 16. (2012). 4) I. Milosevic et al., Appl. Phys. Letters 104, 043701 (2014).

Due to potential technological applications as in data storage [1], catalysis or medicine [2] the structural deformation of uncoated gold nanorods by heat has attracted much scientific attention [3-4]. However, little effort has been made to study the heat-induced deformation behavior of (silica) coated gold nanorods. Coatings of metallic nanoparticles with silica can enhance both the thermal [5] and colloidal stability of the particle and in addition influence the deformation process. Laser-induced deformation experiments for different intensities were conducted and analysed by transmission electron microscopy (TEM) and single-particle electron energy loss spectroscopy (EELS) and were compared to external (oven) heating experiments.
We performed single particle deformation experiments on silica-coated gold nanorods under fs-illumination analyzing both shape and plasmon resonances by electron microscopy. We thereby analyzed the same particles before and after fs-laser pulse excitation. Silica-coated rods were found to be more stable compared to uncoated rods and deform via an intermediate bullet-like
shape. These morphological changes were also reflected in the plasmonic properties as the flat side of the bullet-like particles showed a less pronounced longitudinal plasmon resonance signal. These findings were confirmed by FDTD simulations. Furthermore, size reduction of the particles occured, also for particles that were not completely deformed yet. By comparing the same particles before and after deformation new insight into the deformation process and mechanism can be gained making the modification of single particles in 2D and 3D assemblies possible. Work in progress also includes silica coated core-shell noble metal nanorods [6].

References
[1] P. Zijlstra et al., Nature, 459, 410 (2009)
[2] L.C. Kennedy et al., Small, 7, 169 (2011)
[3] S. Link et al., Journal of Physical Chemistry A, 103, 1165 (1999)
[4] H. Petrova et al., Phys. Chem. Chem. Phys., 8, 814 (2006)
[5] E. Gergely-Fülöp et al., Mater. Chem. Phys., 148, 909 (2014)
[6] T.-S. Deng et al., Chem. Mater., ASAP, doi: 10.1021/acs.chemmater.5b03749 (2015)

Glucose is one of the most important chemicals in biology; it is a basic chemical energy source for many living systems and of great importance in the medical and food processing industries. Today, approximately 40% of all blood tests are related to glucose sensing. Measuring glucose concentrations between 1-10mM is of particular interest because it represents the amount of glucose found in human blood. As such, this concentration range is critical to the diagnosis and management of diabetes.

Here, a glucose-mediated gold nanoparticle (AuNP) synthesis processes, in which the optical absorption peak of the gold nanoparticle solution was found to be linearly dependent on the amount of dissolved glucose present during the nucleation and growth phase is reported. The AuNP synthesis process in this report, was first developed by Zang et al [1] in 2013 and modified to act as a glucose indicator. The process involves the reduction of HAuCl₄ to Au(0) using glucose and MES buffer in an aqueous starch solution at room temperature and neutral pH. This recipe was chosen for its simplicity and low reagent toxicity. Dissolved glucose present during nucleation and growth of Au(0) ranged from 2-10mM, with a resulting absorbance peak shift of 2nm/mM.

The gold nanoparticle fabrication process, optical characterization of the AuNPs, and a proposed mechanism for reduction and nucleation, which accounts for the observed absorption peak shift, will be discussed.

[1] Christian Engelbrekt, Palle S. Jensen, Karsten H. Sørensen, Jens Ulstrup, and Jingdong Zhang. “Complexity of Gold Nanoparticle
Formation Disclosed by Dynamics Study.” J. Phys. Chem. C., 2013, 117, 11818−11828

Superparamagnetic iron oxide nanoparticles (SPIONs) remarkably increase the positive T₁-weighted contrast in magnetic resonance imaging (MRI) and provide a non-toxic alternative to clinically-used heavy metal-based Gadolinium contrast agents. We report the development of a generalized zwitterionic catechol ligand (GZL) synthesis for water-soluble, targeted SPIONs that show no appreciable biofouling. GZLs reported here enable SPION formulations with small enough hydrodynamic diameters to allow for renal clearance while enabling organ-targeting to highlight liver metastases. Furthermore, GZL-ligated SPIONS remain stable to a wide range of pH conditions over long periods of time, providing a novel platform for site-targeted T₁-weighted MRI contrast imaging.

Wei H^†, Bruns OT^†, Kaul M^†, Barch M, Hansen E, Wisniowska A, Chen O, Chen Y, Cordero JM, Okada S, Heine M, Farrar C, Montana D, Adam G, Ittrich H, Jasanoff AP, Bawendi MG. Exceedingly-Small Iron Oxide Nanoparticles as Positive MRI Contrast Agents. (under review, 2015)
Wei H, Insin N, Lee J, Han HS, Cordero JM, Liu W, Bawendi MG. “Compact Zwitterion-Coated Iron Oxide Nanoparticles for Biological Applications.” Nano Letters 2012, 12: 22-25.
Wei H, Bruns OT, Chen O, Bawendi MG. “Compact zwitterion-coated iron oxide nanoparticles for in vitro and in vivo imaging.” Integrative Biology 2013, 5: 108-114.

Self-assembling systems of amphiphilic molecules display structures similar to those of biomineralization natural systems. This allows to somehow mimic nature to synthesize nanomaterials with low polidispersity and with diverse morphologies. In this work we will describe the synthesis and characterization of copper-silver, copper-gold, and silver-gold bimetallic nanoparticles by chemical reduction in self-assembling systems of two surfactants (Cu(AOT)₂ and AOT) stabilizing water-in-oil structures. We also present the behavior of metallic nanoparticles in arsenic removal for water remediation
The synthesized bimetallic nanoparticle average sizes are below 10 nm with polidispersity around 20 %. Single bimetallic nanoparticles studied by Transmission Electron Microscopy-Energy Dispersive Spectroscopy, TEM-EDS, and High Resolution-TEM, are composed of two elements (CuAg, CuAu, and AgAu respectively to each system); these experiments show that the nucleus of the particles are richer in one element than the cortex. This observation is consistent with surface plasmon resonance experiments.
Silicon dioxide (SiO₂) materials were also synthesized; Small Angle X-ray Scattering, SAXS, experiments reveal an hexagonal, SBA15 type mesostructure for SiO₂, which serve as support for the metallic nanoparticle catalysts in water treatment tests. Preliminary results for water remediation in a laboratory controlled experiment show an arsenic removal of 98 % in 340 min.

Surface functionalization has become a pillar of modern colloidal science. The capping molecules - aka ligands - that cover nanoparticles (NPs) can play many different roles. They can control the size and shape of NPs and avoid their aggregation, they can make the NPs compatible with the medium in which they have to be used, they can modulate the physical properties of the core, and they can also bring more specific functions, such as site recognition for targeting in nanomedicine. Accordingly a precise control of the functionalization is of prime importance, yet analyzing in-situ the composition of the ligands shell is an arduous task, especially if the characterization method must be applicable to a wide range of ligands.
In this report, we got interested in thiol stabilized gold NPs, a system that exhibits remarkable properties, especially in plasmonics.¹ A solution ¹H NMR spectroscopy based methodology has been developed to assess quantitatively the composition of the ligands shell of gold NPs protected by two different types of thiols. Ligands with different organic tails (alkyl and aromatic chains, hydrophobic or hydrophilic chains) were studied. By applying this approach to the case of ligands exchange in solution, the relation between the shell and the solution compositions has been experimentally established in different cases. The main finding is that the composition of the ligands shell is generally very different from the one of the solution. Moreover, these measures enabled us building a ligand binding strength scale for several competing ligands. The partition factors determined for different pairs of ligands, as well as the influence of the NPs size, have been rationalized by considering the intermolecular interactions that the ligands can exchange at the surface of the NPs.

1. Charge Transfer at Hybrid Interfaces: Plasmonics of Aromatic Thiol-Capped Gold Nanoparticles. C. Goldmann, R. Lazzari, X. Paquez, C. Boissiere, F. Ribot, C. Sanchez, C. Chaneac, D. Portehault, ACS Nano 2015, 9, 7572-7582.

DNA-stabilized silver clusters (Ag_N-DNA) of 10-30 Ag atoms [1] uniquely combine attributes of both molecular and plasmonic size regimes [1]. Ag_N-DNA with high quantum yield, molecule-like fluorescence [1] exhibit optical properties similar to those of rod-shaped metal nanoparticles. The ability to tailor cluster geometry via DNA sequence makes Ag_N-DNA powerful tools for sensitive biosensing [2], promising fluorescent markers for bioimaging [3], and suitable for DNA-based photonic arrays of atomically precise metal clusters [4]. In addition to a neutral cluster core, Ag_N-DNA contain cationic silver atoms [1] that appear to be central to the relation between DNA sequence and silver cluster structure. However, how the neutral and cationic silver atoms are arranged within the overall Ag_N-DNA nanostructure remains largely unknown.
Here we focus on structurally sensitive circular dichroism (CD) studies of purified Ag_N-DNA [5]. We find similar spectral features across Ag_N-DNAs of neutral cluster core sizes from 4 to 12 atoms, suggesting a similar overall structure despite significant cluster size variations. We find striking similarities between experimental and calculated CD spectra of twisted atomic chains of silver atoms.
To investigate how cationic silver is involved Ag_N-DNA structure we next examine Ag⁺-interactions with homobase oligonucleotides. Ag⁺ uniquely interacts with DNA nucleobases as opposed to the negatively charged phosphate backbone allowing for very specific, tailored binding locations. We find evidence for a previously unreported guanine-Ag⁺-guanine silver-mediated base pairing elucidated from high-resolution electro-spray ionization mass spectrometry [6]. We also find striking similarities in CD spectra between unreduced Ag_N-DNA precursors and Ag⁺-mediated homobase duplexes, suggesting that Ag⁺-mediated base pairing is central to a stable structural foundation for Ag_N-DNAs.

[1] D. Schultz, K. Gardner, N. Oemrawsingh, S. S. R. Markešević, K. Olsson, M. Debord, D. Bouwmeester, and E. Gwinn, Adv. Mater. 25, 2797 (2013).
[2] J. M. Obliosca, C. Liu, and H.-C. Yeh, Nanoscale 5, 8443 (2013).
[3] Y. Antoku, J. Hotta, H. Mizuno, R. M. Dickson, J. Hofkens, and T. Vosch, Photochem. Photobiol. Sci. 9, 716 (2010).
[4] S. M. Copp, D. E. Schultz, S. Swasey, and E. G. Gwinn, ACS Nano 9, 2303 (2015).
[5] S. M. Swasey, N. Karimova, C. M. Aikens, D. E. Schultz, A. J. Simon, and E. G. Gwinn, ACS Nano 8, 6883 (2014).
[6] S. M. Swasey, L. E. Leal, O. Lopez-Acevedo, J. Pavlovich, and E. G. Gwinn, Sci. Rep. 5, 10163 (2015).

We synthesized water-soluble and fluorescent Ag nanoclusters (NCs) stabilized by glutathione at room temperature. Glutathione (GSH) was introduced to increase the stability and water solubility of the Ag NCs. Meanwhile, with this facile approach to synthesis of Ag NCs have surprisingly high efficiency of selective Hg²⁺ sensing, where the limit of detection (LOD) was as low as 10^-10M (0.02 ppb,0.1 nM).This result indicated that using fluorescent Ag NCs as sensor probe to detect Hg²⁺ is a simple and practical strategy.¹ Then using the presynthesized and size-controlled Ag NCs as templates, we synthesized fluorescent gold nanodots (GNDs) with strong fluorescence (quantum yields ∼ 10%), high stability and surface bioactivity by the application of galvanic replacement method.² The as-prepared GNDs have perfect photoluminescence properties with high photo-, time-, metal-, and pH- stability. This is because that the GSH as the ligand protect the GNDs and the presence of Au(I)–S complexes on the surface of the gold core. GSH make GNDs with excellent water solubility and favorable biocompatibility because it is a naturally and readily available tripeptide with carboxyl and amino functional groups. These advantages, combined with their small size, indicate that the as-prepared GNDs have potential application in biological labeling.

Functional polyolefin plastic additive, i.e., maleic anhydride grafted polypropylene (MAPP), has been used as polymeric surfactant for synthesizing magnetic nanostructures via a one-pot in-situ bottom up wet chemistry method. The MAPP was found to serve as stabilizer to stabilize and direct the self assembly patterns/morphology of these magnetic nanostructures. Here, one dimensional nanochains including iron, cobalt, and iron-cobalt alloy will be demonstrated. In addition, the macro-assembly patterns including one-, two-, and three dimensional morphologies will also be presented. The structure manipulation mechanism were studied and the results indicated that it is primarily controlled by the surfactant tail length, capping head density, surfactant-reactant mole ratio, surfactant molecular weight, and surfactant concentration. The force balance by magnetic attraction forces (from magnetic dipolar-dipolar forces) against the repulsive forces (from the steric hindrance of surfactant long chains) were also studied and discussed in detail. The crystalline structures of iron and cobalt nanostructures were also found to be controllable by MAPP with different reaction parameters. The magnetic properties of the synthesized nanostructures will be presented and the difference will also be discussed in detail.