Because applications of nanomaterials in nanomedicine and nanotechnology are rapidly increasing,
nanodiamond (ND) health risk assessment is urgently needed. In the present study, we used HeLa cell model to evaluate
nanodiamond biocompatibility. We found ND-mediated cytotoxicity, proliferation inhibition and oxidative stress. Conversely, ND-associated genotoxicity was limited to higher concentrations used.
Nanodiamond was also recognized as a hypermethylating agent. ND-associated redox imbalance contributed to nucleolar stress: size and number of nucleoli were affected, and release of
nucleolar protein RRN3 occurred. Surprisingly, we did not observe stress-induced
RNA depletion. In contrast,
RNA was stabilized: total
RNA level and integrity (28S/
18S rRNA ratio) were unaffected. After
nanodiamond treatment, upregulation of
DNA methyltransferase 2 (DNMT2) was shown. Perhaps, DNMT2, as a part of the regulatory loop of metabolic pathways through RNA methylation, may contribute to
RNA stabilization and confer stress resistance after
nanodiamond treatment. In conclusion, using HeLa cell model, we showed that ND biocompatibility is limited and special care should be taken when introducing ND-based
biomaterials to biological systems.