Nanodiamonds (NDs) with 5 nm crystalline structures have been recognized as emerging carbon delivery vehicles due to their biocompatible inertness, high surface-to-volume ratio, and energy absorbance properties. In this study, carboxylated nanodiamond (ND-COOH) was reduced to hydroxylated nanodiamond (ND-OH) for stable and pH-independent colloidal dispersity. The poorly water-soluble paclitaxel (PTX) was physically loaded into ND-OH clusters, forming amorphous PTX nanostructure on the interparticle nanocage of the ND substrate. Stable physical PTX loading onto the ND substrate with stable colloidal stability showed enhanced PTX release. ND-OH/PTX complexes retained the sustained release of PTX by up to 97.32% at 70 h, compared with the 47.33% release of bare crystalline PTX. Enhanced PTX release from ND substrate showed low cell viability in Hela, MCF-9, and A549 cancer cells due to sustained release and stable dispersity in a biological aqueous environment. Especially, the IC50 values of ND-OH/PTX complexes and PTX in Hela cells were 0.037 μg/mL and 0.137 μg/mL, respectively. Well-dispersed cellular uptake of suprastructure ND-OH/PTX nanocomplexes was directly observed from the TEM images. ND-OH/PTX nanocomplexes assimilated into cells might provide convective diffusion with high PTX concentration, inducing initial necrosis. This study suggests that poorly water-soluble drugs can be formulated into a suprastructure with ND and acts as a highly concentrated drug reservoir directly within a cell.

Nanodiamonds have been discovered as a new exogenous material source in biomedical applications. As a new potent form of nanodiamond (ND), polyamidoamine-decorated nanodiamonds (PAMAM-NDs) were prepared for E7 or E6 oncoprotein-suppressing siRNA gene delivery for high risk human papillomavirus-induced cervical cancer, such as types 16 and 18. It is critical to understand the physicochemical properties of siRNA complexes immobilized on cationic solid ND surfaces in the aspect of biomolecular structural and conformational changes, as the new inert carbon material can be extended into the application of a gene delivery vector. A spectral study of siRNA/PAMAM-ND complexes using differential scanning calorimetry and circular dichroism spectroscopy proved that the hydrogen bonding and electrostatic interactions between siRNA and PAMAM-NDs decreased endothermic heat capacity. Moreover, siRNA/PAMAM-ND complexes showed low cell cytotoxicity and significant suppressing effects for forward target E6 and E7 oncogenic genes, proving functional and therapeutic efficacy. The cellular uptake of siRNA/PAMAM-ND complexes at 8 h was visualized by macropinocytes and direct endosomal escape of the siRNA/PAMAM-ND complexes. It is presumed that PAMAM-NDs provided a buffering cushion to adjust the pH and hard mechanical stress to escape endosomes. siRNA/PAMAM-ND complexes provide a potential organic/inorganic hybrid material source for gene delivery carriers.

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