Symposium NT5 : Nanodiamonds---Fundamentals and Applications

Understanding interactions between nanodiamonds (NDs) and their environment is critical to develop new NDs applications. Aqueous environment necessitates particular attention since its influence on NDs properties is poorly understood while most of applications in nanomedicine, environmental science or photocatalysis take place in such media. Unfortunately, the influence of aqueous environment, especially when it is related to electronic processes, cannot be investigated in liquid with classical methods.

In this presentation, I will present how synchrotron-based soft x-ray absorption, emission and photoemission spectroscopies can overcome the challenge of measuring electronic structure of nanomaterials directly in aqueous environment. Using X-ray absorption spectroscopy, modification of the NDs surface chemistry induced by aqueous dispersion was recently evidenced.¹ Furthermore, a significant impact of nanodiamonds on the water organization in their solvation shell was also observed.² Future directions implementing these methods to follow electro- and photochemical reactions at the surface of NDs and other carbon nanomaterials in liquid environment will be discussed.

References

1. Petit, T.; Pflüger, M.; Tolksdorf, D.; Xiao, J.; Aziz, E. F. Valence Holes Observed in Nanodiamonds Dispersed in Water. Nanoscale 2015, 7, 2987–2991.
2. Petit, T.; Yuzawa, H.; Nagasaka, M.; Yamanoi, R.; Osawa, E.; Kosugi, N.; Aziz, E. F. Probing Interfacial Water on Nanodiamonds in Colloidal Dispersion. J. Phys. Chem. Lett. 2015, 6, 2909–2912.

Photothermal (PTS) and photoacoustic (PAS) spectroscopies belong to calorimetric methods of absorption spectroscopy. They complement transmission spectroscopy as the signals in PTS/PAS are directly governed by the heat converted by the analyzed system under the excitation irradiation: i.e. the light absorption of chromophores and the heat distribution in the system. Being significantly more sensitive than the majority of methods of absorption spectroscopy and giving multiple signals of various nature from a single measurement, they are relevant for simultaneous estimation of light-absorption and thermophysical properties of various materials, especially for materially or optically heterogenous systems. The progress in laser technologies brings microscopical optical schemes of PTS/PAS into practice.
In this study, PTS/PAS were used for characterizing nanodiamond (ND) sols (dispersions) in aqueous and organic media. The motivation of this study is the fact that many relevant ND properties as materials, nanofluids, or biolabels depend on their production and purification technologies, and it is strongly necessary to know both the ND concentration and distribution and their primary particle and aggregate sizes. Thus, we used PTS/PAS in multiwavelength, transient, and scanning modes and in meso- and microscopic scales for physicochemical analysis and the estimation of thermophysical properties of ND dispersions from 20 trademarks from various manufacturers. The schematics and details of PTS/PAS measurements will be provided.
The estimation of ND concentrations at subnanogram amounts by PTS is shown. Extinction spectra of ND aqueous dispersions by conventional absorption spectroscopy and PAS differ significantly, and the contributions from absorption and scattering were estimated by their comparison. PTS/PAS multispectral data were correlated with the results from other methods: DSC, dynamic laser scattering (DLS), X-ray diffraction, and UV-spectroscopy.
Key thermophysical properties of ND dispersions as nanofluids—thermal diffusivity, thermal effusivity, and thermal conductivity—were estimated from PTS (thermal-lens) data, and their values were compared with pure solvents and other types of nanofluids. These parameters were measured in dynamic (time-resolved transient response profiles of thermal-lens signals) and batch (amplitude) modes of PTS. Several PTS methods and their applicability towards this aim will be compared.
Imaging of thin layers of samples of ND dispersions showed a significant difference in the spatial distribution and cluster size for various ND trademarks. As a whole, thermal lensing reveals clusters of ca. 50–200 nm in ND aqueous dispersions. The estimation of the cluster size from two techniques—transient and imaging PTS–results in concordant values and agree with DLS data, which is rather invigorating for further investigations.
This study was supported by NUST MISiS (grant no K3-2015-064, M.P.) and RFBR (grant no. 16-33-60147, D.V.)

This work investigates the colloidal interactions and rheological behavior of nanodiamond (ND) dispersions, which is critical for its use in composite materials. While ND represents a promising class of nanofiller due to its high surface area, superior mechanical strength, optical transparency, tailorable surface functionality and biocompatibility, much remains unknown about the behavior of ND dispersions and their responses to various processing conditions. We hypothesize that controlling interactions in ND dispersions will allow for developing systems with tunable modulus and shear response. Steady and dynamic rheology experimental techniques are thus used to systematically investigate systems of nanodiamonds dispersed in model polar and non-polar media and examine the microstructure and concomitant rheological behavior.

We find that ND forms gels almost instantaneously in a non-polar media, the strength of which follows a power-law behavior. In contrast, ND in polar media show a time-dependent behavior with the modulus increasing with time. We attribute the difference in behavior to the variation in inter-particle interactions as well as the interaction of the ND with the media. Large steady and oscillatory strains are applied to ND colloidal gels to investigate the role of shear in gel microstructure breakdown and recovery. For colloidal gels in non-polar medium, the incomplete recovery of elastic modulus at high strain amplitudes indicates dominance of particle-particle interactions; however, in polar media the complete recovery of elastic modulus even at high strain amplitudes indicates dominance of particle-solvent interactions. These results taken together provide a platform to develop self-supporting gels with tunable properties in terms of ND concentration, and solvent type.

Nanodiamonds are aggregates of primary polyhedral sp³ carbon-based particles of around 3 nm in diameter. The particles ae wrapped by graphitic or amorphous carbon layers, showing some chemical functionalities on the surface. It is known that dried diamonds are highly hygroscopic.¹ Generally speaking sp²-based carbons show a hydrophobic nature and presence of micropores and small mesopores induce a kind of transformation from hydrophobicity to hydrophilicity with growth of water clusters.^2-4 On the other hand, the edge-carbon rich carbon shows a hydrophilicity in the lower water vapor pressure range.⁵ Then, we need to understand the hydrophilic nature of nano diamonds with relevance to the nano porosity. The comparative study of water adsorption on nano diamonds and graphitic nano porous carbons will be presented.
We used nanodaiamond samples supplied by NanoAmando Hard Hydrogel. The nano diamonds of 3 nm in the average primary size were used without further purification. Nitrogen adsorption isotherms at 77 K and water vapor adsorption at 298 K were measured after outgassing at 423, 523, and 623 K. The surface chemistry of the samples was examined with XPS and TPD.
The nitrogen adsorption isotherms indicated the presence of micropores of 0.1 ml/g and mesopores of 0.35 ml/g, which do not change so much with the outgassing at different temperature. The water adsorption isotherms showed hydrophobicity below P/P₀ = 0.3 and hydrophilicity above P/P₀ = 0.5. The water adsorption isotherms are quite similar to nano porous sp²-based carbons, although XPS and TPD show the presence of surface functional groups.

References
1. M. V. Korovov, M. M. Batuk, N. V. Avramenko, N. I. Ivanova, N. N. Rozhkova, E. Osawa, Diamond Relate. Mater. 2010, 19, 665-672.
2. T. Ohba, H. Kanoh, K. Kaneko, Nano Lett, 2005, 5, 227-230.
3. K. Kaneko, Nature Chem. 2015, 7, 194-197.
4. E. Zoraida pina-Salazar, K. Kaneko, Colloid Interface Sci. Comm. 2015, 5, 8-11.
5. M. Asai, T. Ohba, T. Iwanaga, H. Kanoh, M.Endo, J. Campos-Delgado, M. Terrones, K. Nakai, K. Kaneko, J. Amer. Chem. Soc. 2011, 133,
14830-14833.

Disintegration and size. Several methods have been found to break up the commercial agglutinates of detonation nanodiamond (often offered as primary particles), but the only scalable one is attrition milling of agglutinate powder suspended in water with zirconia microbeads as attritter. Optimization of a large set of operation conditions in attrition milling posed a formidable challenge during the initial phase of our work, but adaptation of Taguchi’s method of quality engineering in 2013 finally gave us pure black and clear ‘solution’ of PPDND with an average diameter of 2.8±0.5 nm. Thus, previously reported size of 4-5 nm could be due to incomplete disintegration to give mostly dimers, which are the product of the coherent interfacial Coulombic interactions between oppositely charged facets between a couple of PPDND.
Unique properties. We have already mentioned above on the strong electrostatic fields on the surface when the old size data of PPDND were given new interpretation. We believe this unusual feature of permanent polarization as the most important feature to understand various new features in PPDND. Here we mention only one example of unique behavior in PPDND. When we succeeded in the production of concentrated (up to 5 wt%) but well dispersed aqueous colloidal solution of PPDND, we thought the dispersion will be more stable upon dilution, but the reverse was true: the more we dilute, the larger became particle size as measured by DLS method. This new phenomenon, ‘dispersion by concentration, aggregation by dilution’ can be interpreted by invoking the colloid crystal known in colloidal chemistry: well hydrated colloids are known to exhibit periodical distribution of colloidal particles in water.
Perspectives. Due to many new properties and behaviors of PPDND that we have never seen in chemistry, a number of novel applications can be readily expected. We are currently developing three potential applications: (1) as drug carriers for cancer chemotherapy, (2) as rolling spacers in a new lubricant system named nanospacer lubrication, and (3) as a Hall-Petch toughening component in solid materials like thermoplastic polymers. Preliminary tests showed much more encouraging results for all three uses compared to conventional reinforcements.

Aggregates of detonation nanodiamond (DND) have long been of interest for their numerous potential applications; however, no size of DND is perhaps more elusive, yet technologically important, than sub 10 nanometer (or “single-digit”) primary particles. Primary particles of DND have a number of potential applications including drug delivery, seeding in microelectronics, polymer nanocomposites, and lubricants. Nevertheless, the challenge associated with obtaining these particles from the 200-300nm aggregates of purified detonation soot has made them too expensive for widespread use. Even after overcoming the initial challenge of obtaining the primary particles, they are still often limited in their use due to the random assortment of chemical functional groups found on their surface. Therefore, an additional challenge is to gain control over the ability to tailor the surface chemistry of the particles without sacrificing their size by promoting aggregation. A final challenge is to identify useful solvents where stability and size of the functionalized particles are preserved. Here we report our work in obtaining high yields of 5nm primary particles of DND, progress made toward functionalizing these particles with a number of useful chemical structures including: amines, hydrophobic chains, and N-Hydroxysuccinimide (NHS), and the dispersion of these particles in a range of solvents such as DMSO, NMP, DMF, THF, ethylene glycol, synthetic oils, alcohols, and water.

Many models of detonation nanodiamond show a partially aromatic surface layer, which should give a significant spectroscopic signature since a complete aromatic shell of a 5-nm diameter particle would contain nearly 25% of all carbon [1]. However, ¹³C nuclear magnetic resonance (NMR) shows ≤ 1% of aromatic carbons in pristine purified detonation nanodiamond [1, 2]. Instead, the surface is found to be covered by C-H, C-OH, and a few C=O moieties. The 12-14% surface carbons (i.e. those with bonds to ≤3 carbons) expected for a bulk-terminated diamond particle are thus accounted for [1]. NMR, unlike many other spectroscopies, including IR, Raman, and XANES, is intrinsically quantitative, with fractional peak areas equal to the fraction of carbons in the respective chemical environment, so that carbon percentages can be determined without an external standard. In addition, peak positions in NMR are more systematically related to structure than, for instance, in Raman spectroscopy, where quite recently the “graphitic” peak of nanodiamond at 1620 cm^-1 was reassigned to OH bending vibrations [3]; the intensity loss of this band with heat treatment [4] confirms its assignment to OH moieties. Unlike NMR, XPS cannot resolve a distinct peak of a few percent of aromatic carbons.[5] Reviewing literature data from previous studies by NMR and other methods, including HRTEM, XPS, Raman, and XANES [6, 1, 7], we will demonstrate that none of these investigations have documented an aromatic fraction of >2% in pristine, properly purified detonation nanodiamond. Time permitting, other NMR-derived structural aspects of nanodiamond particles, such as the nonaromatic core–shell structure [2] and the depth of N and of unpaired electrons [2] from the surface will also be reviewed.

[1] Cui, J.-F.; Fang, X. W.; Schmidt-Rohr, K. Quantification of C=C and C=O Surface Carbons in Detonation Nanodiamond by NMR; J. Phys. Chem. C 2014, 118, 9621-9627.
[2] Fang, X.; Mao, J.; Levin, E. M.; Schmidt-Rohr, K. Nonaromatic Core-Shell Structure of Nanodiamond from Solid-State NMR Spectroscopy; J. Am. Chem. Soc. 2009, 131, 1426-1435.
[3] Mochalin, V.; Osswald, S.; Gogotsi, Y. Contribution of Functional groups to the Raman Spectrum of Nanodiamond Powder; Chem. Mater. 2009, 21, 273-279.
[4] Chen, J.; Deng, S. Z.; Chen, J.; Yu, Z. X.; Xu, N. S. Graphitization of Nanodiamond Powder Annealed in Argon Ambient; Appl. Phys. Lett. 1999, 74, 3651-3653.
[5] Butenko, Y. V.; Krishnamurthy, S.; Chakraborty, A. K.; Kuznetsov, V. L.; Dhanak, V. R.; Hunt, M. R. C.; Šiller, L. Photoemission Study of Onionlike Carbons Produced by Annealing Nanodiamonds; Phys. Rev. B 2005, 71, 07542
[6] Panich, A. M. Nuclear Magnetic Resonance Studies of Nanodiamonds; Crit. Rev. Solid State Mater. Sci. 2012, 37, 276-303.
[7] Schmidt-Rohr, K., Cui, J. Reply to a Comment on “Quantification of C=C and C=O Surface Carbons in Nanodiamond by NMR”; J. Phys. Chem. C 119, 21288–21291 (2015).

Fluorescent nanodiamonds are becoming increasingly important in applications of bio-labeling and bio-imaging as well as quantum information processing and nanophotonics. This stems primarily from their unprecedented bio-compatibility and the ability to host bright fluorescent color centers.
In this talk, I will first give a brief introduction into the field of fluorescent nanodiamonds and in particular the generation of luminescent defects. In particular, I will focus on two interesting candidates – the silicon vacancy and the nitrogen vacancy color centers. I will describe how these centers are fabricated and will highlight the importance of surface modification to control and manipulate the emission properties.
I will then describe two approaches to enhance luminescence from single emitters in nanodiamonds. The first includes a single step biological coating with metalo-organic complexes that results in an enhancement of emission. This process is bio-compatible and can be easily use to achieve strong contrast of bright florescent nanodiamonds. The second approach involves a facile self assembly method to couple nanodiamonds hosting single nitrogen vacancy defects to plasmonic resonators. Controlled attachment to the apexes is realized and transmission through the silver nanowire is achieved.
I will then summarize and present a promising outlook for future directions in fluorescent nanodiamonds.

The negatively charged nitrogen-vacancy center (NV^–) in Fluorescent Nanodiamond (FND) is an atom-like emitter with unique magneto-optical properties. Its fluorescence can be magnetically modulated, allowing for background-free detection. Here, we scrutinize this property and illustrate its potential use by applying a periodic, time-varying magnetic field to FND-containing solutions and tissue sections with lock-in detection. It is shown that ultra-sensitive mass determination of FNDs in water can be achieved at a concentration lower than 50 ng/mL, with a magnetic field strength of 200 G and a modulation frequency of 10 Hz. This enables high-sensitivity quantification of the uptake of FNDs by cells and the biodistribution of FND-labeled cells in a mouse model. The utility and versatility of the technique are further demonstrated with an application to acquire high contrast images by wide-field microscopy of FND-labeled cells in mouse tissue sections.

Nanodiamonds have been utilized for a broad spectrum of drug delivery and imaging applications with marked enhancements in efficacy and safety [1-3]. For example, the administration of nanodiamond-doxorubicin (NDX) complexes towards breast, liver, and brain cancer therapy has resulted in substantial improvements in drug tolerance and decreased systemic and localized toxicity. In addition, nanodiamond-gadolinium complexes have mediated one order of magnitude improvements in per-gadolinium relaxivity. Recently, nanodiamonds have been used to reinforce various polymeric devices including contact lenses and other platforms to enable lysozyme-triggered drug release for potential applications in glaucoma therapy [4]. Nanodiamond incorporation into these devices simultaneously enhanced the mechanical robustness of the device while also sustaining oxygen and water content properties, indicating no adverse effects upon potential wear comfort. Following the demonstration of improved monotherapy using nanodiamond drug delivery, it is becoming increasingly important to develop optimized nanomedicine-enhanced combination therapy. However, conventional approaches utilize additive dosing, which serves as a major barrier towards the systematic identification of drug-dose ratios that can realize globally optimal efficacy and safety of treatment. Our recent work has demonstrated that a powerful mechanism-independent technology platform, termed Phenotypic Personalized Medicine.Drug Development (PPM.DD) is capable of rapidly optimizing nanodiamond-modified as well as unmodified drug combinations based upon experimentally-validated data [5]. This approach will result in markedly-improved response rates to treatment through the rational combinatorial therapy design.

References

[1] Mochalin et al., Nature Nanotechnology, 2012.
[2] Chow et al., Science Translational Medicine, 2011.
[3] Chow et al., Science Translational Medicine, 2013.
[4] Kim et al., ACS Nano, 2014.
[5] Ho et al., Science Advances, 2015.

Nanodiamond (ND)-mediated drug delivery has been of increasing interest due to its improved circulatory half-life, increased retention time within target cell, and decreased unintended cytotoxic effects and incidence of resistance. However, numerous challenges exist regarding implementation of ND mediated drug delivery for nanomedicine purposes such as optimizing drug combinations loaded onto ND and translational studies of ND nanotechnology to the human system. Thus, we developed an optimization method platform for drug combination therapy to achieve higher efficacy and demonstrated ND-mediated material in a human system model for future development of translational research.
Combinatorial chemotherapeutic drug treatment is currently used to improve efficacy for cancer treatment. However, no simple and systematic method exists to optimize the efficacy of drug combinations. Therefore, we developed Feedback System Control II (FSC II), an engineering-based screening approach; FSC II is a method that finds optimum drug combinations by converging towards the global maximum of a quadratic dose response surface constructed from the phenotypically driven drug efficacy vs drug dose data in a mechanism-independent manner. In the study, 57 randomly selected combinations of Doxorubicin, Mitoxantrone, and Bleomycin incorporated ND-drug complexes and unmodified Paclitaxel were applied on three cancer cell lines (MDB-MB-231, BT-20, and MCF-7) and three control cell lines (MCF-10A, IMR-90, and H9C2) to construct a quadratic surface map from therapeutic windows (viability of controls - viability of cancer) and drug dose information. Optimum drug combinations were then obtained by a differential evolution optimization protocol. Thus, verification of FSC II was demonstrated by optimized ND-drug complex combinations outperforming ND-mediated and unmodified single drug, randomly sampled unoptimized ND-drug complex, and optimal unmodified drug combination therapies.
Additionally, we demonstrated the model of composite materials containing ND-drug in a human system for translational research. When teeth are badly decayed or infected, the infected nerves and pulps are removed and replaced by a rubbery compound called gutta-percha to save the teeth and prevent further infection. However, teeth can get re-infected, resulting in retreatment of the root canal and/or replacement of infected teeth with expensive dental implants. Therefore, we explored ND-mediated amoxicillin combined with regular gutta-percha composite (1,4-trans-polyisoprene, ZnO₂, BaSO₄, and wax), which effectively killed Staphylococcus aureus, one of the bacteria responsible for root canal re-infection. Furthermore, the ND-mediated amoxicillin gutta-percha composite was mechanically stronger than regular gutta-percha.
With these recent advances of our research, the necessary improvements of ND-mediated drug therapies were demonstrated to achieve sustainable nanomedicine purposes within humans.

While advances have improved the overall treatment of cancer, liver cancers continues to be difficult to treat with liver cancer annual deaths continuing to rise. Our lab has shown that specific genomic alterations can influence drug sensitivity or resistance as well as targetable markers. Understanding the therapeutically targetable molecular mechanisms of specific liver cancer molecular subtypes has allowed us to intelligently design personalized nanodiamond-based drug delivery and imaging complexes for these specific molecular subtypes. Nanodiamonds (NDs) are ~4nm carbon nanoparticles with a truncated octahedral structure. We and others have show that nanodiamonds are a versatile drug delivery platform that can be functionalized with a broad array of molecules, including small molecules, proteins and genetic material, with a high level of biocompatibility. We have shown enhanced efficacy and safety of ND-anthracycline drug delivery complexes against a number of cancer models in vitro and in vivo. This included being able to enhance treatment of MYC-driven chemoresistant cancer stem cells and prevent secondary tumor formations in vivo. We have also explored the mechanisms by which ND-anthracycline drug delivery occurs at both the system and cellular level and identified several key mechanisms that contribute to enhanced drug retention, cancer cell specific drug release as well as lower systemic drug toxicity that can be applied to a wide range of other nanomedical applications for improved drug delivery. Beyond anthracyclines, we have now fabricated targeted dual-drug delivery ND complexes to delivery new classes of drugs, including mTOR and MEK inhibitors, against AKT/RAS-driven liver tumors. Additionally, we have evaluated the use of NDs as a platform for SALL4-driven tumor tissue selective therapeutic delivery and drug release. These recent advances in ND drug delivery of new classes of therapeutics as well as enhanced mechanisms of tumor specific drug delivery further demonstrate the potential for a ND-based platform for the development of personalized drug-delivery or imaging complexes as we have now demonstrated improved efficacy and/or safety against several specific liver cancer molecular subtypes.

Nanomaterials hold tremendous potential in addressing the two major issues faced by our society: providing energy and improving healthcare. Nanodiamond powder produced by detonation and readily available in commercial quantities for moderate price, is one of the most promising carbon nanomaterials for theranostics. Made of ~5 nm diamond particles with large accessible surface and tailorable surface chemistry, it has unique optical, mechanical and thermal properties, and is non-toxic. These properties have recently started to attract much interest among researchers working on different biomaterials and drug delivery systems. For tissue engineering scaffolds, the non-toxic fluorescent nanodiamond introduced into biodegradable polymers provides increased strength, visual monitoring, and enhanced biomineralization. In drug delivery, the rational surface modification of nanodiamond allows for enhanced adsorption and chemical binding of the drugs for sustained or triggered drug release. In the area of biomedical imaging and diagnostics, luminescent nanodiamond with NV centers, as well as chemically modified fluorescent nanodiamond, hold tremendous potential to replace toxic semiconductor quantum dots, thus bringing this exciting potential application one step closer to the clinics. The purification, characterization and surface modification of nanodiamond for biomedical applications will be discussed in detail. Recent progress in development of nanodiamond-containing biodegradable polymer scaffolds for tissue engineering and bone surgery will be reviewed. Surface modifications of nanodiamond for drug delivery exploiting adsorption/desorption mechanisms will be discussed, with illustrations of the use of adsorption/desorption data for rational design of the nanodiamond surface for optimal drug delivery platforms.

Common anti-inflammatory drugs are used as short-term relief to reduce inflammation. However, they have many undesirable off-target effects, including weakening of the adaptive immune system. By attaching these drugs to nanoparticles, we hypothesize that we will be able to selectively target macrophages, a specific type of innate immune cell that has a high potential for nanoparticle uptake, thus reducing off-target effects and increase drug efficacy. By designing nanoparticles with dual therapeutic and diagnostic, or theranostic, properties, we can create an optimized drug delivery system to be used to target and track disease progression and treatment in patients with chronic inflammation. Nanodiamond (ND) is a highly versatile carbon nanomaterial, which exhibits such properties as chemical stability, and low cytotoxicity. Because of its surface, which is covered with charged functional groups, ND properties are easy to tune, allowing for the ability to create multimodal nanoparticles. In this work, we demonstrated the therapeutic potential of this system by adsorbing a model drug, dexamethasone, to the surfaces of two different types of modified ND and determined their adsorption isotherms/desorption curves in order to determine optimal conditions. We found that hydrophobic ND with octadecylamine attached to its surface (ND-ODA) has superior adsorptive properties compared to hydrophilic, carboxylated ND (ND-COOH). We also took advantage of ND-ODA’s intrinsic blue fluorescence by monitoring its uptake in and effect on human macrophages by using fluorescent microscopy and immunohistochemistry. Together, these results demonstrate the potential for ND-ODA to aid in the targeted delivery of dexamethasone to macrophages. Further studies include optimizing the drug delivery system in vitro to control macrophage behavior as well as confirm preferential uptake in macrophages compared to other cell types.

Delivery of therapeutics into central neural system (CNS) is complicated by the need for the drugs to cross the blood-brain barrier (BBB). Polymer nanoparticles in the past have been demonstrated as efficient carriers of anesthetics and other drugs across the BBB. However, it is very difficult to produce polymer nanoparticles of very small size (~5 nm) with narrow size distribution and with highly tailorable surface chemistry necessary for delivery of various types of drugs. Thus, there is no single polymer that would work in all situations. In this research, we developed non-toxic nanodiamond particles (ND) with highly tailorable surface chemistry based on commercial inexpensive NDs produced by detonation. We performed in vitro studies of adsorption/desorption of DOX on NDs with different surface chemistries to get more insights into mechanisms and parameters governing these processes, and used this knowledge to identify the NDs which perform optimally in terms of the drug loading and binding strength. The developed NDs have then been tested in vivo as drug delivery vehicles for doxorubicin (DOX) in treatment of human glioma in the nude mice animal model. Doxorubicin, as well as many other anticancer chemotherapeutics, is extremely difficult to deliver across the BBB when the drug is injected intravenously. In contrast to pure DOX, the ND-DOX complexes injected intravenously showed much higher efficiency in treatment of the human glioma model. At the same time, ND-DOX toxicity to the animals was significantly lower compared to Temozolomide - one of a few drugs available for treatment of glioma