Targeting and non-targeting effects of nanomaterials on DNA: challenges and perspectives

Due to their large-scale manufacture and widespread application, there have been a number of studies related to toxicological assessment of nanomaterials (NMs) over the past decade. Although there has been extensive research on the cytotoxicity of NMs, concerns have been raised about their possible genotoxicity. The genome is constantly exposed to genotoxic insults that can lead to DNA damage, which in turn can have consequences for health, such as the induction of carcinogenesis. This comprehensive review focuses on the direct and indirect interactions of NMs with DNA. Factors influencing the genotoxicity of NMs, such as their physicochemical characteristics, are also discussed. The mechanisms involved in the direct and indirect interactions of NMs with DNA are also reviewed. Many studies have shown that ENMs have genotoxic effects, such as chromosomal fragmentation, DNA strand breaks, point mutations, oxidative DNA adducts, apoptosis, hypoxic responses, mitochondrial dysfunction, and epigenetic modifications. As the data reported to date are inconsistent, it is difficult to draw definitive conclusions regarding the features of NMs that promote genotoxicity. Therefore, challenges and future research perspectives are discussed. This review provides insights into the genotoxic effects of NMs and their consequences for human health.