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size, nanodiamonds are classified into nanocrystalline particles (1–150 nm), ultrananocrystalline particles (2–10 nm) and diamondoids (1–2 nm) [17]. These nanocrystalline and ultracrystalline diamonds are superior to silicon, platinum nanoparticles
in biomedical implants coating due to their superior mechanical and wear-resistant
properties. They possess low cytotoxicity and have high roughness, dense structure,
and surface binding capacity [18, 19].
2.1 NDs as a Drug Delivery Agent
Nanodiamonds (NDs) are an ideal tool for conjugation of biomolecules via chemical
bonding or physical adsorption due to their large surface to volume ratios, improved
cellular delivery, the formation of loose clusters, and biocompatibility. NDs were
conjugated with doxorubicin hydrochloride (DOX) via ionic forces in an aqueous
medium and were used as a delivery agent. These DOX loaded NDs formed loose
aggregates, which reduced the systemic adverse effects of plain DOX [20]. In another
study, 10- hydroxycamptothecin (HCPT) was adsorbed on the surface of NDs via
physical forces, which resulted in enhanced release of HCPT in the phosphatebuffered saline medium. The Nds-HCPT complex showed a 2.5% increase in cytotoxicity to HeLa cells than the plain chemotherapeutic agent HCPT [21]. Hence,
it can be stated that drugs loaded on NDs improve the pharmaceutical properties
of the drugs. Thus, the usage of NDs based delivery agent could overcome the use
of a high dosage of chemotherapeutic drugs in cancer treatment and overcome the
drawbacks of the chemotherapeutic drugs. In another study, conjugation of NDs
with hydroxypolyethyleneglycol-4000 via covalent bond was performed, and later
DOX was adsorbed on the surface of conjugated nanodiamond (ND-PEG-DOX).
This formulation was used to treat human liver cancer cells, and the study reported
efficient delivery of the formulation via clathrin-dependent pathways. The results
also demonstrated that the half-life of this conjugate was double than free DOX
uptake, and the DOX detached from the conjugate and entered into the nucleolus to
stop the cell proliferation [22].
2.2 In Gene Therapy
Apart from acting as drug delivery agents, NDs efficiently deliver biological
molecules such as DNA, RNA, and proteins. These nanodiamonds serve as a safe
and effective method of gene therapy in comparison to viral gene therapy. It was
reported that insulin when adsorbed on the surface of these nanodiamonds in a pHdependent system at pH 10.5 via physical forces, the release of insulin was 20 times
higher than the neutral pH system. This suggests that the aggregation properties of
the insulin improved upon interacting with NDs [23, 24]. To the best of our knowledge, it is known that the biomolecules could not be delivered directly into the cells
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