Literatura académica sobre el tema "Nanodiamond (ND)"

The quest for active, yet “green” non-toxic catalysts is a continuous challenge. In this work, covalently linked hybrid porphyrin–nanodiamonds were prepared via ipso nitro substitution reaction and characterized by X-ray photoelectron spectroscopy (XPS), fluorescence spectroscopy, infrared spectroscopy (IR) and thermogravimetry-differential scanning calorimetry (TG-DSC). The amine-functionalized nanodiamonds (ND@NH2) and 2-nitro-5,10,15,20-tetra(4-trifluoromethylphenyl)porphyrin covalently linked to nanodiamonds (ND@βNH-TPPpCF3) were tested using Allium cepa as a plant model, and showed neither phytotoxicity nor cytotoxicity. The hybrid nanodiamond–copper(II)–porphyrin material ND@βNH-TPPpCF3-Cu(II) was also evaluated as a reusable catalyst in cyclohexene allylic oxidation, and displayed a remarkable turnover number (TON) value of ≈265,000, using O2 as green oxidant, in the total absence of sacrificial additives, which is the highest activity ever reported for said allylic oxidation. Additionally, ND@βNH-TPPpCF3-Cu(II) could be easily separated from the reaction mixture by centrifugation, and reused in three consecutive catalytic cycles without major loss of activity.

A stirring mill, an ultrasonic bath and a high-speed shearing emulsifier were adopted to modify the surface characteristics of nanodiamond (ND) respectively. The ζ-potential, size distribution and Fourier transform infrared spectroscopy (FT-IR) of ND were measured to evaluate its properties. Results show that the ζ-potential of ND modified with SHP (either by Mechano-chemical Modification or Ultrasonic measurement) drops sharply. Results also show that the rotating speed of the emulsifier exerts little influence on the size D5 but great influence on the size D95 of ND.

In this work, we have introduced a carbon nanomaterial (nanodiamond), to bind with anticancer drug doxorubicin (DOX) with via amide bond conjugation for cancer drug delivery and therapy. Nanodiamond (ND) was initially carboxylated by the surface modification along the treatment with strong alkaline solution (H2SO4:HNO3) and then activated the carboxyl moiety of ND with the addition of EDC. Anticancer drugs were bound to the ND through a succession of chemical modifications by adipic acid dihydrazide (ADH). The ND-Drug conjugate was analyzed by Nuclear Magnetic Resonance (1H-NMR) Spectroscopy, Fourier Transform Infrared (FTIR) Spectroscopy and Mass Spectroscopy (MS), Atomic Force Microscopy (AFM), Particle size, Zeta potential, Drug release, SRB assay against MCF-7 cells, and DNA fragmentation. Spectroscopic analysis confirms the conjugation of nanodiamond with different anticancer drug. AFM photomicrograph represents the surface morphological features of ND-DOX conjugates. In- vitro investigation showed that ND-DOX conjugates have slow and sustained drug release characteristics. In-vitro cytotoxicity studies, an enormous cytotoxic potential of ND-Drug conjugates were showed against cancer cell line. Above all findings were suggested that the ND-DOX conjugates may be a potential inhibitor of MCF-7 cancer cells to act as a drug candidate. According to all these data it can be confirm that the ND-DOX conjugates could be an effective agent for drug delivery and could be promising in future for tumor targeting strategy. Keywords: Nanodiamond, Sustained Release, Drug Delivery, Cytotoxicity, Conjugates

Nanomaterials can intensively scatter and/or reflect radiation. Such processes and materials are of theoretical and practical interest. Here, we study the quasi-specular reflections (QSRs) of cold neutrons (CNs) and the reflections of very cold neutrons (VCNs) from nanodiamond (ND) powders. The fluorination of ND increased its efficiency by removing/replacing hydrogen, which is otherwise the dominant cause of neutron loss due to incoherent scattering. The probability of the diffuse reflection of VCNs increased for certain neutron wavelengths by using appropriate ND sizes. Based on model concepts of the interaction of CNs with ND, and in reference to our previous work, we assume that the angular distribution of quasi-specularly reflected CNs is narrower, and that the probability of QSRs of longer wavelength neutrons increases if we increase the characteristic sizes of NDs compared to standard detonation nanodiamonds (DNDs). However, the probability of QSRs of CNs with wavelengths below the cutoff of ~4.12 Å decreases due to diffraction scattering on the ND crystal lattice. We experimentally compared the QSRs of CNs from ~4.3 nm and ~15.0 nm ND. Our qualitative conclusions and numerical estimates can help optimize the parameters of ND for specific practical applications based on the QSRs of CNs.

A chemically conjugated nanodiamond (ND)/MoS2 nanocomposite was synthesized with amine-functionalized MoS2 and acyl chloride-coordinated ND. The chemical structure and morphology of the nanocomposite were characterized to examine the dispersion of MoS2 on the ND platform. The results revealed that the degree of dispersion was enhanced with increasing ratio of MoS2 nanosheets to ND. Moreover, the nanosheets consisted of several molecular interlayers that were well-dispersed on the ND platform, thereby forming a nanophase. The efficient electrocapacity of the ND/MoS2 nanocomposite was considerably greater than that of the MoS2 electrode alone. Furthermore, the nanophase distribution of MoS2 on ND with a graphitic shell provided a large surface area and reduced the diffusion distance of ions and electrons. Therefore, the nanophase electrode showed higher electrochemical capacitance than that of the MoS2 electrode alone.

Electron paramagnetic resonance (EPR) and electron spin echo (ESE) at X-band (9.4 GHz) and W-band (94 GHz) have been used to study defects in natural diamond nanocrystals, detonation nanodiamond (ND) with a size of  4.5 nm and detonation ND after high-pressure high-temperature (HTHP) sintering with a size of  8.5 nm. Based on identification of atomic nitrogen centers N0 and nitrogen pairs N2+ detected by means of the high frequency EPR and ESE in natural diamond nanocrystals, atomic nitrogen centers N0 have been discovered in nanodiamond core in detonation ND and detonation ND after sintering. In addition EPR signal of multi-vacancy centers with spin 3/2 seems to be observed in diamond core of detonation ND.

In this study, to achieve a homogeneous dispersion of nanodiamond (ND) in a polyimide (PI) matrix and a strong interfacial adhesion between ND and the PI matrix, a biomimetic nondestructive dopamine chemistry was employed for surface modification of ND.

Nanodiamond prepared by detonation synthesis using explosives as the precursor exhibits serious agglomeration characteristics in non-polar medium such as clean oil. Mechanochemical measures were introduced to modify nanodiamond (ND) surface, improve its dispersion behavior and actualize suspension stability. Hyperdispersants’s adsorption can be intensified with the participations of mechanical forces, and the main mechanism of hyperdispersant may lie in the steric stabilization of its adsorption layer founded on ND surface. After the eagglomeration and dispersion treatments, a suspension containing ND particles with the average diameter of around 55 nm can be prepared and it can be reserved for over 6 months without any sedimentation.

Nanomechanical characterization of micrometric fibers of polyaniline (PANI) doped with nanodiamond (ND) particles resulting from the self-assembling of PANI/ND nano-fibrils has been performed using torsional harmonics atomic force microscopy.

In this work, several optical-spectroscopic methods have been used to visualize and investigate the penetration of diamond nanoparticles (NPs) of various sizes (3–150 nm), surface structures and fluorescence properties into the animal skin in vitro. Murine skin samples have been treated with nanodiamond (ND) water suspensions and studied using optical coherence tomography (OCT), confocal and two-photon fluorescence microscopy and fluorescence lifetime imaging (FLIM). An analysis of the optical properties of the used nanodiamonds (NDs) enables the selection of optimal optical methods or their combination for the study of nanodiamond–skin interaction. Among studied NDs, particles of 100 nm in nominal size were shown to be appropriate for multimodal imaging using all three methods. All the applied NDs were able to cross the skin barrier and penetrate the different layers of the epidermis to finally arrive in the hair follicle niches. The results suggest that NDs have the potential for multifunctional applications utilizing multimodal imaging.

To fully exploit the capability of NV centers in diamond as magnetic sensors and quantum bits, the optimum production recipe as well as the method to enhance its optical performance has been studied in this work. The NV centers in bulk diamond were prepared by ion implantation and electron irradiation, and the optimum dose and temperature are found by comparing its optical and magnetic performance both experimentally and theoretically. In addition, the enhancement of optical performance and size characterization of NV centers in nanodiamonds will be discussed in this work.

Nanophotonic circuits for single photon emitters. The work demonstrated in this thesis is dedicated to the engineering, simulation, fabrica-tion and investigation of the essential element base to develop hybrid fully integrated nanopho-tonic circuit with coupled single photon emitter on chip. Combining several individually opti-mized stages of photonic devices, interconnected by nanoscale waveguides on chip with eva-nescently coupled single photon emitter, is a key step to the realization of such a scheme. The main requirements which should be satisfied for building such a hybrid system on-chip, and are thus the subject of this Thesis, are, namely: integration of single photon photostable source with high Quantum Yield (QY) on chip, efficient coupling of the emitted light to nanophotonic cir-cuits, and efficient filtering of the excitation light. Silicon nitride-on-insulator was used in all the projects described in this Thesis as the platform for the realization of photonic circuits. It provides low-loss broadband optical transparency covering the entire visible range up to the near infrared spectrum. Furthermore, sufficiently high refractive index contrast of Si3N4 on SiO2 enables tight confinement of the mode in the waveguide structure and the realization of photonic circuits with small footprint. A drastic increase of the coupling efficiency of the emitted light into the waveguide mode can be achieved by placing single-photon emitter on photonic crystal cavity because of its high Quality factor and small mode volume enabling a high Purcell enhancement. To this end, a novel cross-bar 1D freestanding photonic crystal (PhC) cavity was developed for evanescent integration of single photon emitter, in particular Nanodiamonds (NDs), onto the region of the cavity. The novelty of this photonic structure is that collection of emitted light is provided via waveguide, which consists of PhC, whereas direct optical excitation is obtained through a crossed waveguide in the orthogonal direction of the in-plane cavity. Optimization of the PhC cavity architecture was performed via rounds of simulations and ver-ified by experimental measurements of fabricated devices on chip, which were found in excel-lent agreement. The next round of simulations was performed to define an optimal position of the source in the cavity region to achieve maximum Purcell enhancement, which was realized via Local Density of States (LDOS) computation. Thus, placing a single photon emitter into a determined position on the cavity region of the developed cross-bar 1D freestanding PhC enables an increase in the transmission coupling efficiency into cavity up to =71% in comparison with computed 41% in the case of coupling into waveguide mode of cross-bar structure without PhC. To block the pump light and at the same time transmit the fluorescent emitted light, compact and low-loss cascaded Mach–Zehnder interferometers (MZIs) tunable filters in the visible region embedded within nanophotonic circuit, were realized. Tunability was provided via thermo-optic effect. The design of this device, namely geometry and shape of the microheater, was optimized via thermo-optic measurements, to achieve low electrical power consumption (switching power of 12.2 mW for the case of a spiral-shape microheater), high filtration depth and low optical insertion loss. The novel design with double microheaters on top of both arms of single and cascaded MZIs allows doubling the range of the shifting amplitude of the interference fringes. The demonstrated architecture of tunable filter is multifunctional, namely allowing transmission and filtering of the desired wavelengths in a wide wavelength range. In particular, filtration depth beyond 36.5 dB of light with 532 nm wavelength and simultaneous transmission of light with 738 nm wavelength, which correspond respectively to excitation and emission wavelength of the silicon-vacancy color center in diamond, was demonstrated. The results were published in Ovvyan, A. P.; Gruhler, N.; Ferrari, S.; Pernice, W. H. P. Cascaded Mach-Zehnder interferometer tunable filters. Journal of Optics 2016, 18, 064011 https://doi.org/10.1088/2040-8978/18/6/064011 Another filter with non-repetitive stopband with bandwidth of several nanometers was developed in this thesis. A non-uniform Bragg grating filter with novel double Gaussian apodization was proposed, whose fabrication required a single lithography step. This optimized Bragg filter provides a 21 dB filtration depth with a 3-dB bandwidth of 5.6 nm, insuring negligible insertion loss in the best case, while averaged insertion loss in reflected signal is 4.1dB (including loss in splitter). One of the first Hybrid organic molecule Dibenzoterrylene (DBT) coupled on chip to a nanophotonic circuit was demonstrated in this thesis. DBT is a photostable single photon source in the near infrared spectrum at room and at cryogenic temperature, with almost unitary quan-tum yield. In order to protect the molecule against oxidization DBT was embedded in a host matrix – thin Anthracene crystal (DBT:Ac), which increases photostability. Mirror enhanced grating couplers were employed as convenient output ports for ridge Si3N4 waveguide to detect single photons emitted from integrated Dibenzoterrylene (DBT) molecules at room temperature. The coupling ports were designed for waveguide structures on transparent silica substrates for light extraction from the chip backside. These grating ports were employed to read out optical signal from waveguides designed for single-mode operation at λ=785 nm. DBT molecule was coupled evanescently to the waveguide, and upon excitation of isolated single molecule, emitted single photon signal was carried inside the waveguide to the outcou-pling regions. Using a Hanbury Brown and Twiss setup pronounced antibunching dip was read out from a single molecule via the grating couplers, which confirms the quantum nature of the outcoupled fluorescent light. Simulated and measured transmission coupling efficiency of sin-gle photon emission into the waveguide mode equals =42%. The results were published in P. Lombardi*, A. P. Ovvyan*, S. Pazzagli, G. Mazzamuto, G. Kewes, O. Neitzke, N. Gruhler, O. Benson, W. H. P. Pernice, F. S. Cataliotti, and C. Toninelli. Photostable Molecules on Chip: Integrated Sources of Nonclassical Light. ACS Photonics 2018, 5, 126−132, DOI: 10.1021/acsphotonics.7b00521. * P. Lombardi and A. P. Ovvyan contributed equally to this work. Engineered nanophotonic elements integrated in optical circuits with coupled single photon emitter on chip allow simultaneously to enhance the emitted light by coupling it into resonant PhC cavity modes, to spatially separate the excitation light from the enhanced single photon emission and to filter out pump light. Enhancement of the emission rate leads to a sig-nificant increase of the coupling efficiency into cavity. Beforehand performed simulations were an essential step in order to design, build and optimize the architecture of the nanophotonic devices. Local Density of States enhancement computation was especially necessary to pre-cisely determine optimized position of the source on PhC cavity region to obtain maximum enhancement of the emission rate. To evaluate transmission coupling efficiency of emitted light into the cavity (β-factor), an extra round of simulations was performed. The integrated photonic elements investigated and optimized in this Thesis, will be further employed for the realization of hybrid photonic circuits with integrated single photon sources: silicon-vacancy, nitrogen-vacancy centers in diamond as well as single organic molecule and semiconducting single-walled carbon nanotubes.

Nanofluid is the suspension formed by lubricating oil and nanoparticles with particles sizes of 1~100 nm, and common nanoparticles include metal nanoparticles (Cu, Ag, etc.), oxide nanoparticles (Al2O3, SiO2, ZrO2, etc.), carbides (CNT, diamond), and MoS2 nanoparticles, etc. Different nanoparticles exhibit various physicochemical properties (e.g., structure and shape), which can influence their tribological characteristics. In this work, six nanofluids, namely, MoS2, SiO2, diamond, carbon nanotubes (CNTs), Al2O3, and ZrO2, were used as minimum quantity lubrication grinding fluids to select the kind of nanoparticles with optimum lubrication performance in grinding nickel alloy GH4169. Experimental results concluded the following: 1) Nanoparticles with spherical or sphere-like molecular structure and nanofluids with high viscosity demonstrate superior lubrication performances. 2) The polishing effect of nanodiamond particles enhances their surface morphology. 3) The lubricating property of the six nanofluids is described in the following order: ZrO2 < CNTs < ND < MoS2 < SiO2 < Al2O3.

Biopolymers have a great potential in biomedical engineering, having been used as scaffolds for hard and soft tissues, such as bone and blood vessels for many years. More recently biopolymers have also found applications in surgical fixation devices. Compared with conventional metal fixation devices, bone grafts and organ substitutes, biopolymer products have advantages of no long-term implant palpability or temperature sensitivity, predictable degradation to provide progressive bone loading and no stress shielding, all of which leads to a better bone healing, reduced patient trauma and cost, elimination of second surgery for implant removal, and fewer complications from infections. However lack of initial fixation strength and bioactivity are two major concerns which limited more widespread applications of biopolymers in orthopedic surgery. Nanodiamond is attractive for its use in reinforcement of composite materials due to their outstanding mechanical, chemical and biological properties. Nanotechnology shows us many innovations and it is generally accepted view that many could be further developed and applied in tissue engineering. In this work, we conduct poly(L-lactic acid) (PLLA) and octadecylamine functionalized nanodiamond (ND-ODA) composite research to optimize the polymer/ND interface, thus to reinforce the mechanical strength. Composites comprising PLLA matrix with embedded ND-ODA were prepared by mixing PLLA/chloroform solution with chloroform suspension of nanodiamonds at concentrations of 0–10 by weight percent. The dispersion of ND-ODA was observed by transmission electron microscopy (TEM). TEM micrographs show that ND-ODA can disperse uniformly in PLLA till 10% wt. Nanoindentation result shows the mechanical strength of ND-ODA/PLLA composites improving following increasing the concentration of ND-ODA in composites. The noncytotoxicity of ND-ODA was demonstrated on 7F2 Osteoblasts. To test the usefulness of ND-ODA/PLLA composites as scaffolds for supporting cell growth, 7F2 Osteoblasts were cultured on scaffolds for 6 days. The attachment and proliferation of 7F2 on all scaffolds were assessed by fluorescent nuclear staining with Hoechst 33258 and Alamar BlueTM assay. The results showed that the adding ND-ODA does small influence cell growth, which indicates the composites have good biocompatibility. The morphology of 7F2 cells growing on all ND-ODA/PLLA composite scaffolds was determined by SEM, which confirms the Osteoblasts spread on the scaffolds. All these results combined suggest that ND-ODA/PLLA might provide a novel composite suitable for surgical fixation devices.

Nanodiamond (ND) is an attractive nanomaterial for reinforcement of biopolymers due to the ND’s superior mechanical and chemical properties, and low biotoxicity. A novel composite material has been produced for bone scaffolds utilizing the biodegradable polymer poly(L-lactic acid) (PLLA) and octadecylamine-functionalized nanodiamond (ND-ODA). Composites were prepared by admixing to a PLLA/chloroform solution chloroform suspension of ND-ODA in concentration range of 0–10% (w/w). The dispersion of ND-ODA evaluated by transmission electron microscopy (TEM) shows uniform distribution of ND-ODA in PLLA matrix. The composites were characterized by differential scanning calorimetry (DSC). DSC analysis of the composites showed no significant thermal behavior changes with the addition of ND-ODA into the polymer. Biomineralization test shows that ND-ODA can enhance the mineral deposition on scaffolds. Improved mechanical properties and good biocompatibility with enhanced biomineralization combined suggest that ND-ODA/PLLA might have potential applications for bone tissue engineering.

It has been demonstrated from recent research that nanodiamond(ND)-enabled drug delivery as cancer therapeutics represents an important component of optimized device functionality. The goal of the current research is to develop a multiscale modeling technique to understand the fundamental mechanism of a ND-based cancer therapeutic drug delivery system. The major components of the proposed device include nanodiamonds (ND), parylene buffer layer and doxorubicin (DOX) drugs, where DOX loaded self-assembled nanodiamonds are packed inside parylene capsule. The efficient functioning of the device is characterized by its ability to precisely detect targets (cancer cells) and then to release drugs at a controlled manner. The fundamental science issues concerning the development of the ND-based device includes (a) a precise identification of the equilibrium structure, surface electrostatics and self assembled morphology of nanodiamonds, (b) understanding of the drug/biomarker adsorption and desorption process to and from NDs, (c) rate of drug release through the parylene buffers, and finally, (d) device performance under physiological condition. In this study, we aim to systematically address these issues using a multscale computational framework. Specifically, the structure and electrostatics of the functionalized NDs are predicted by quantum scale calculation (Density Functional Tight Binding). The DFTB) study on smaller NDs suggests a facet dependent charge distributions on ND surfaces. Using the charges for smaller NDs (∼ valid for 1–3.3 nm dia ND), we then determined surface charges for larger (4–10 nm) truncated octahedral nanodiamonds (TOND). We found that the [100] face and the [111] face contain positively and negatively charged atoms, respectively. Employing this surface electrostatics of nanodiamonds, atomistic-scale simulations are performed to simulate the self-assembly process of the NDs and drug molecules in a solution as well as to evaluate nanoscale diffusion coefficient of DOX molecules. In order to quantify the nature of the aggregate morphology, a fractal analysis has been performed. The mass fractal dimensions for a variety of aggregate size have been obtained from molecular simulations assuming ‘diffusion-limited aggregation (DLA)’ process. Then, by considering the experimentally observed aggregate dimensions, by using DLA based fractal analysis and by utilizing Lagvankar-Gemmell Model for aggregate density, a continuum model for larger aggregates will be developed to characterize aggregate strengths and break-up mechanism, which in turn will help us to understand how aggregate size can be reduced. In this talk, an outline for this continuum model will be discussed. In addition, we have been performing molecular simulations on DOX-ND where multiple drug molecules are allowed to interact with a cluster of self-assembled nanodiamonds in pH controlled solution. The purpose of this study is to find the effect of solution pH on the loading and release of drug to and from nanodiamonds. Our initial results show that a higher pH is necessary to ensure drug release from nanodiamonds. Once we completely understand the essential physics of pH controlled drug loading and release, we plan to develop multiscale models of tumor nodules to represent them as a collection of individual tumor cells. Each cell will be then modeled as a deformable body comprised of three homogenous materials: cortex membrane, cytosol and nucleus. The cortex membrane and the cytosol will serve as a weak permeable medium where the absorption coefficients of the doxorubicin remain constant and obey Fick’s law. In this study, it will be assumed that drug release from the microdevice to its outer periphery will be governed by Fickian Diffusion. It will also be assumed that the complex flow of drug through the interstitial fluid of the body will be dictated by Darcy’s law. It will be assumed that the solute drug transport in these regions will be due to a combination of convection, diffusion, elimination in the intra- and extra-cellular space, receptive cell internalization and degradation. Results from this study will provide fundamental insight on the definitive targeting of infected cells and high resolution controlling of drug molecules.

Nanotechnology shows us many innovations and it is generally accepted view that many could be further developed and applied in tissue engineering. A novel composite material has been produced for bone scaffolds utilizing the biodegradable polymer poly(L-lactic acid) (PLLA) and octadecylamine functionalized nanodiamond (ND-ODA). The composites were characterized by hardness testing (Rockwell) and differential scanning calorimetry (DSC). DSC analysis of the composites showed no significant thermal behavior changes when adding ND into the polymer matrix. Rockwell result shows ND-ODA improves mechanical strength of composites 4 folds. To test the usefulness of ND-ODA/PLLA as a matrix for supporting cell growth, 7F2 Osteoblasts were cultured on scaffolds for 3 days. The results showed that the addition of ND-ODA has almost no influence on cell growth, which indicates the composites are biocompatible. All these results combined suggest that ND-ODA/PLLA might provide a novel composite suitable for bone tissue engineering application.

Nanodiamond (ND) is an attractive nanomaterial for reinforcement of polymers [1] due to the ND’s superior mechanical and chemical properties, and low biotoxicity. A novel composite material has been produced for bone scaffolds utilizing the biodegradable polymer, poly(L-lactic acid) (PLLA), and octadecylamine-functionalized nanodiamond (ND-ODA) [2]. Composites were prepared by admixing to a PLLA/chloroform solution chloroform suspensions of ND-ODA at concentrations of 0, 1, 3, 5, 7, and 10 (w/w). Dispersion of ND-ODA in the composites was studied by transmission electron microscopy (TEM). The lower-resolution TEM micrograph of 1% wt ND-ODA/PLLA film (Fig. 1a) shows nanodiamond particles dispersed in PLLA film on amorphous carbon support. Due to long hydrocarbon chains of ODA the ND-ODA particles have good wettability with the PLLA so there is no segregation of ND-ODA and PLLA, and the polymer completely surrounds the particles. The high-resolution TEM image (Fig. 1b) shows ND crystals with attached organic material that can be ODA or PLLA. Nanoindentation tests show that the mechanical strength of ND-ODA/PLLA composites improves upon addition of ND (Table 1). Even at low concentrations (1% wt) the ND-ODA increased the hardness of the composite by 60% and Young’s modulus by 20% over neat PLLA. Based on our preliminary observations, we conclude that further additions of ND-ODA resulted in smaller changes with subsequent saturation in the mechanical properties at ∼7% wt (see Table 1). ND is relatively novel nanomaterial. Establishing its biocompatibility requires further studies, especially for modified ND. We studied the biocompatibility of 5–10nm ND and ND-ODA in experiments with a murine osteoblast cell line (7F2, from ATCC). Incubation of a cultured osteoblasts with 1–100μg/ml of ND or ND-ODA particles for 4 hours did not show much influence on the cell viability (Fig. 2), as inferred from an alamarBlue™ assay. To test the feasibility of ND-ODA/PLLA as a matrix material supporting cell growth, osteoblasts were cultured on the composites for 6 days. The attactment and proliferation of 7F2 cells on the scaffolds were assessed, respectively, by fluorescent nuclear staining with Hoechst 33258 and the alamarBlueTM assay. Our results showed that the addition of ND-ODA had only a negligibly small effect on cell proliferation, which is indicative of good biocompatibility of the composites (Fig. 3). The morphology of 7F2 cells growing on all ND-ODA/PLLA composite scaffolds was assessed by SEM. The data (not shown) confirm that the osteoblasts spread on the scaffolds similar to their spreading on TCP (tissue culture plastic). To summarize, the improved mechanical properties of the PLLA/ND-ODA composites and their good biocompatibility suggest that these materials may be suitable for applications in musculoskeletal tissue engineering.

Porous poly(lactic acid) PLA materials are highly demanded as scaffolding templates in tissue engineering applications. In this study, a protocol for creating co-continuous porous PLA structures with nanodiamond (ND) as additive was investigated. First, a ternary blend of PLA/PS/ND was prepared with different mixing ratios under different mixing conditions. Next, a post annealing stage was applied to coarsen the phase structure. Finally, the PS phase was sacrificially extracted, leaving a porous matrix. The experimental results showed that ND can be an effective compatiblizer for increasing the miscibility between PS and PLA and reducing the phase size. It was further found that the post annealing conditions significantly affect the distribution of ND particles in the blend and finally in the porous PLA structure.

Several reports have described the relationship between size, aspect ratio, surface modification and internalization for a variety of nanoparticles (i.e. gold, polymer, carbon nanotubes). Nanodiamonds (NDs) in particular have recently been implicated in a variety of biomedical applications. One of the most promising is in utilizing NDs as drug delivery carriers where successful internalization is of utmost importance. A few reports recently have demonstrated the energy dependent internalization of bare NDs. In this report, we investigate the internalization mechanism and kinetics of functional ND-conjugate translocation.

While cancers have no known cure, some of them can be successfully treated with the combination of surgery and systematic therapy. In general, systemic/widespread chemotherapy is usually injected into the bloodstream to attempt to target cancer cells. Such procedure often imparts devastating side effects because cancer drugs are nonspecific in activity, and transporting them throughout the bloodstream further reduces their ability to target the right region. This means that they kill both healthy and unhealthy cells. It has been observed that the physiological conditions of the fluids around living cells can be characterized by pH, and the magnitude of pH around a living cell is different from cancerous cells. Moreover, a multiscale anatomy of carcinoma will reveal that the microstructure of cancer cells contains some characteristic elements such as specific biomarker receptors and DNA molecules that exclusively differentiate them from healthy cells. If these cancer specific ligands can be intercalated by some functional molecules supplied from an implantable patch, then the patch can be envisioned to serve as a complementary technology with current systemic therapy to enhance localized treatment efficiency, minimize excess injections/surgeries, and prevent tumor recurrence. The broader objective of our current research is to capture some fundamental insights of such drug delivery patch system. It is envisioned that the essential components of the device is nanodiamonds (ND), parylene buffer layer and doxorubicin (DOX) drugs. In its simplest form, self-assembled nanodiamonds - functionalized or pristine, and DOX molecules are contained inside parylene capsule. The efficient functioning of the device is characterized by its ability to precisely detect targets (cancer cells) and then to release drugs at a controlled manner. The fundamental science issues concerning the development of the ND-based device include: 1. A precise identification of the equilibrium structure and self assembled morphology of nanodiamonds, 2. Fundamental understanding of the drug adsorption and desorption process to and from NDs, and 3. The rate of drug release through the parylene buffers. The structure of the nanodiamond (ND) is crucial to the adsorption and desorption of drug molecules because it not only changes the self-assembly configuration but also alters the surface electrostatics. To date, the structure and electrostatics of NDs are not yet well understood. A density functional tight binding theory (DFTB) study on smaller [2] NDs suggests a facet dependent charge distributions on ND surfaces. These charges are estimated by Mulliken Analysis [1]. Using the charges for smaller NDs (∼valid for 1–3.3 nm dia ND) we first projected surface charges for larger (4–10 nm) truncated octahedral nanodiamonds (TOND), and it has been found that the [100] face and the [111] face contain positively and negatively charged atoms, respectively. These projected charges are then utilized to obtain the self assembled structure of pristine TONDs from Molecular Dynamics (MD) simulations [4] as shown in Fig. 1. The opposite charges on the [100] and [111] face invoked electrostatic attractions among the initially isolated NDs and a network of nanodiamond agglutinates are formed as evidenced in Fig. 1(b). This study confirms why as manufactured NDs are found in agglomerated form. The study also suggests that a large fraction of ND surfaces become unavailable for drug absorption as many of the [100] faces are coherently connected to [111] faces. As a result, it can be perceived that effective area for drug adsorption on ND surfaces will be less compared to theoretical prediction which suggests that a 4nm TOND may contain as high 360 drug molecules on its surface [5]. It has been observed that as manufactured NDs may contain a variety of functional groups, and currently, we are studying the mechanism of self-assembly for functionalized nanodiamonds so that we understand the role of functional groups. The next phase of calculation involves binding of the DOX to the NDs. Essentially, the understanding of drug absorption and desorption profile at a controlled rate to and from NDs is the most critical part of the device design. Some recent quantum calculation suggests that part of NDs and drug molecules contain opposite charges at their surfaces; it has been a natural interpretation that interactions between ND and drug molecules should be straight-forward — NDs should attract to drugs as soon as they come closure. Recent experiments [6], however, suggest that NDs usually do not interact with drug molecules in the presence of neutral solutions. Addition of NaCl in the solution improves the interaction dramatically. In the first part of the study, we [3–5] have studied the interaction of single DOX molecules with TOND surfaces via MD simulation. As shown in Fig. 2, this study suggests that DOX molecules first arrange them around the preferential sites on nanodiamonds (e.g. around the [111] face) and then spontaneously attach on the surface. It is also observed that only DOX molecule is attached per facets of TONDs. It can be noted that each TOND has 6 [100] face and 8 [111] faces. Figure 3 shows the energy minimization process during the DOX-ND interaction. It can be noted that these simulations have been performed in vacuum environment. In order to see how DOX interacts in solution media, another set of simulations have been conducted where “vacuum” environment have been replaced with solution media of different pH. Moreover, functionalization on the ND surfaces will create a different environment for the DOX molecules. Research is underway to capture the fundamental physics on the DOX loading and release to and from functionalized nanodiamonds. Once we understand the essential physics of drug loading and unloading, in the future we plan to model diffusion controlled drug release through ND coated film device by incorporating the multiscale science learned from the current study. Results from this study will provide fundamental insight on the definitive targeting of infected cells and high resolution controlling of drug molecules.

The goal of this work is to gain fundamental understanding of the surface structure of functionalized detonation nanodiamonds (NDs) using quantum mechanics (QM) based multiscale modeling and simulation. The study entails a multiscale approach to bridge the length scale between the real sizes of ND being fabricated (∼4 nm) and the size allowed by employing first-principles based modeling (< 1 nm). At first, the structure of NDs of technologically relevant size (∼4 nm) was optimized using classical mechanics based molecular mechanics simulations. QM based density functional theory (DFT) was then employed to simulate the structure and analyze the properties of relevant parts of the optimized cluster. This work is extended to NDs functionalized with carboxylic acid (-COOH) and carbonyl oxygen (=O), which help to guide further experiments on functionalization of NDs and their use as carriers of drug molecules to the desired site.