Enhancing chemotherapeutic efficiency through improved drug delivery would facilitate treatment of chemoresistant cancers, such as recurrent mammary tumors and liver cancer. One way to improve drug delivery is through the use of nanodiamond (ND) therapies, which are both scalable and biocompatible. Here, we examined the efficacy of an ND-conjugated chemotherapeutic in mouse models of liver and mammary cancer. A complex (NDX) of ND and doxorubicin (Dox) overcame drug efflux and significantly increased apoptosis and tumor growth inhibition beyond conventional Dox treatment in both murine liver tumor and mammary carcinoma models. Unmodified Dox treatment represents the clinical standard for most cancer treatment regimens, and NDX had significantly decreased toxicity in vivo compared to standard Dox treatment. Thus, ND-conjugated chemotherapy represents a promising, biocompatible strategy for overcoming chemoresistance and enhancing chemotherapy efficacy and safety.
Finely divided carbon particles, including charcoal, lampblack, and diamond particles, have been used for ornamental and official tattoos since ancient times. With the recent development in nanoscience and nanotechnology, carbon-based nanomaterials (e.g., fullerenes, nanotubes, nanodiamonds) attract a great deal of interest. Owing to their low chemical reactivity and unique physical properties, nanodiamonds could be useful in a variety of biological applications such as carriers for drugs, genes, or proteins; novel imaging techniques; coatings for implantable materials; and biosensors and biomedical nanorobots. Therefore, it is essential to ascertain the possible hazards of nanodiamonds to humans and other biological systems. We have, for the first time, assessed the cytotoxicity of nanodiamonds ranging in size from 2 to 10 nm. Assays of cell viability such as mitochondrial function (MTT) and luminescent ATP production showed that nanodiamonds were not toxic to a variety of cell types. Furthermore, nanodiamonds did not produce significant reactive oxygen species. Cells can grow on nanodiamond-coated substrates without morphological changes compared to controls. These results suggest that nanodiamonds could be ideal for many biological applications in a diverse range of cell types.
Nanodiamond materials can serve as highly versatile platforms for the controlled functionalization and delivery of a wide spectrum of therapeutic elements. In this work, doxorubicin hydrochloride (DOX), an apoptosis-inducing drug widely used in chemotherapy, was successfully applied toward the functionalization of nanodiamond materials (NDs, 2-8 nm) and introduced toward murine macrophages as well as human colorectal carcinoma cells with preserved efficacy. The adsorption of DOX onto the NDs and its reversible release were achieved by regulating Cl- ion concentration, and the NDs were found to be able to efficiently ferry the drug inside living cells. Comprehensive bioassays were performed to assess and confirm the innate biocompatibility of the NDs, via real-time quantitative polymerase chain reaction (RT-PCR), and electrophoretic DNA fragmentation as well as MTT analysis confirmed the functional apoptosis-inducing mechanisms driven by the DOX-functionalized NDs. We extended the applicability of the DOX-ND composites toward a translational context, where MTT assays were performed on the HT-29 colon cancer cell line to assess DOX-ND induced cell death and ND-mediated chemotherapeutic sequestering for potential slow/sustained released capabilities. These and other medically relevant capabilities enabled by the NDs forge its strong potential as a therapeutically significant nanomaterial.
Gene therapy holds great promise for treating diseases ranging from inherited disorders to acquired conditions and cancers. Nonetheless, because a method of gene delivery that is both effective and safe has remained elusive, these successes were limited. Functional nanodiamonds (NDs) are rapidly emerging as promising carriers for next-generation therapeutics with demonstrated potential. Here we introduce NDs as vectors for in vitro gene delivery via surface-immobilization with 800 Da polyethyleneimine (PEI800) and covalent conjugation with amine groups. We designed PEI800-modified NDs exhibiting the high transfection efficiency of high molecular weight PEI (PEI25K), but without the high cytotoxicity inherent to PEI25K. Additionally, we demonstrated that the enhanced delivery properties were exclusively mediated by the hybrid ND-PEI800 material and not exhibited by any of the materials alone. This platform approach represents an efficient avenue toward gene delivery via DNA-functionalized NDs, and serves as a rapid, scalable, and broadly applicable gene therapy strategy.
A new facile method that employs high‐power sonication is used to break up firmly agglutinated nanodiamonds and obtain dispersion just as effectively as stirred‐media milling. The dispersion properties of the de‐agglutinated nanodiamonds in various nonaqueous solvents, and the pH‐dependent dispersion/precipitation behavior of the hydrosols are presented (see figure). The brownish color of the colloids is attributed mostly to the Rayleigh scattering superimposed over the finite absorption in the visible wavelength.
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