The enormous therapeutic potential of RNA interference (RNAi) has long been recognized. While efficient small interfering RNA (siRNA) delivery vectors exist, many sacrifice biocompatibility, which can challenge their applicability as a therapeutic agent. Nanodiamonds (NDs) represent promising strategies for efficient siRNA delivery given the multitude of beneficial properties integrated into one platform that include uniform particle sizes, material scalability, the ability to carry nearly any type of therapeutic, and preserved biocompatibility, among others. Here we present a broadly applicable ND delivery platform that demonstrates biocompatible siRNA delivery with enhanced efficacy in media, signifying the translational potential of this approach. SECTION Nanoparticles and Nanostructures

Nanodiamonds (NDs) are promising candidates in nanomedicine, demonstrating significant potential as gene/drug delivery platforms for cancer therapy. We have synthesized ND vectors capable of chemotherapeutic loading and delivery with applications towards chemoresistant leukemia. The loading of Daunorubicin (DNR) onto NDs was optimized by adjusting reaction parameters such as acidity and concentration. The resulting conjugate, a novel therapeutic payload for NDs, was characterized extensively for size, surface charge, and loading efficiency. A K562 human myelogenous leukemia cell line, with multidrug resistance conferred by incremental DNR exposure, was used to demonstrate the efficacy enhancement resulting from ND-based delivery. While resistant K562 cells were able to overcome treatment from DNR alone, as compared with non-resistant K562 cells, NDs were able to improve DNR delivery into resistant K562 cells. By overcoming efflux mechanisms present in this resistant leukemia line, ND-enabled therapeutics have demonstrated the potential to improve cancer treatment efficacy, especially towards resistant strains.

Functional groups and their associated charges are responsible for the binding and release of molecules from the surfaces of particles in nanodiamond colloids. In this work, we describe a combined set of experimental and computational techniques that are used to characterize these functional groups quantitatively. The surfaces of the particles examined during this study are amphoteric, as one would expect for surfaces made of carbon, with high concentrations of phenols, pyrones, and sulfonic acid groups; the average 50-nm-diameter nanodiamond aggregate has approximately 22000 phenols, 7000 pyrones, and 9000 sulfonic acids. The aggregates also have at least 2000 fixed positive charges, stabilized within pyrones and/or chromenes. No evidence for a significant concentration of carboxylic acid groups was found, although some are probably present. Hydroxyl and epoxide groups are present on some areas of the surfaces. The surfaces are graphitized, so the presence of phenols and pyrones is not surprising because such groups are common on graphitic surfaces. The sulfonic acid is due to the sulfuric acid treatment used to remove amorphous carbon and graphite during particle cleaning. The fixed charges are also due to the cleaning procedure that includes the use of KMnO 4 with the sulfuric acid.Based on titration and zeta potential experiments, elemental and particle size analyses, and modeling using semiempirical quantum mechanics, a model is proposed for the types and concentrations of surface groups. The modeling shows how functional groups form during the bead milling and cleaning used in the preparation of the colloid. It also shows that the pK a associated with the phenols and pyrones that are formed (pK a = 7.6−10.0) is consistent with that predicted using titration experiments (pK a ≥ 7.3). The positive surface potential means that the latter pK a value is significantly larger than a Henderson− Hasselbalch-based estimate. The model is shown to be useful in explaining a number of recent experiments in which nanodiamonds were used to bind and release therapeutic drug and polymer molecules.

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Nanodiamonds (NDs) are versatile nanoparticles that are currently being investigated for a variety of applications in drug delivery, biomedical imaging and nanoscale sensing. Although initial studies indicate that these small gems are biocompatible, there is a great deal of variability in synthesis methods and surface functionalization that has yet to be evaluated. Here we present a comprehensive analysis of the cellular compatibility of an array of nanodiamond subtypes and surface functionalization strategies. These results demonstrate that NDs are well tolerated by multiple cell types at both functional and gene expression levels. In addition, ND-mediated delivery of daunorubicin is less toxic to multiple cell types than treatment with daunorubicin alone, demonstrating the ability of the ND agent to improve drug tolerance and decrease therapeutic toxicity. Overall, the results here indicate that ND biocompatibility serves as a promising foundation for continued preclinical investigation.