Due to the widespread applications of zinc oxide nanoparticles (ZnO NPs), the potential exposure of workers, consumers, and scientists to these particles has increased. This potential for exposure has attracted extensive attention in the science community. Many studies have examined the toxicological profile of ZnO NPs in the immune system, digestive system, however, information regarding the toxicity of ZnO NPs in the nervous system is scarce. In this study, we detected the cytotoxicity of two types of ZnO NPs of various sizes – ZnO a NPs and ZnO b NPs – and we characterized the shedding ability of zinc ions within culture medium and the cytoplasm. We found that reactive oxygen species played a crucial role in ZnO NP-induced cytotoxicity, likely because zinc ions were leached from ZnO NPs. Apoptosis and cytoskeleton changes were also toxic responses induced by the ZnO NPs, and ZnO b NPs induced more significant toxic responses than ZnO a NPs in SHSY5Y cells. In conclusion, ZnO NPs induced toxic responses in SHSY5Y cells in a size-dependent manner, which can probably be attributed to their ion-shedding ability.

The pharmacological potential of nanotechnology, especially in drug delivery and bioengineering, has developed rapidly in recent decades. Ion channels, which are easily targeted by external agents, such as nanomaterials (NMs) and synthetic drugs, due to their unique structures, have attracted increasing attention in the fields of nanotechnology and pharmacology for the treatment of ion channel-related diseases. NMs have significant effects on ion channels, and these effects are manifested in many ways, including changes in ion currents, kinetic characteristics and channel distribution. Subsequently, intracellular ion homeostasis, signalling pathways, and intracellular ion stores are affected, leading to the initiation of a range of biological processes. However, the effect of the interactions of NMs with ion channels is an interesting topic that remains obscure. In this review, we have summarized the recent research progress on the direct and indirect interactions between NMs and ion channels and discussed the related molecular mechanisms, which are crucial to the further development of ion channel-related nanotechnological applications. 1 | INTRODUCTION With the rapid development of nanotechnology, the biological effects of nanomaterials (NMs), ranging in size from 1-100 nm, size range have attracted substantial attention (Ou et al., 2016; L. Wang, Hu, & Shao, 2017). Because of their high surface energy, volume effects, and quantum size effects, NMs have prospective applications in biomedical fields, including biomedical imaging (Rosado-de-Castro,

Autophagy is a biological process that has attracted considerable attention as a target for novel therapeutics. Recently, nanomaterials (NMs) have been reported to modulate autophagy, which makes them potential agents for the treatment of autophagy‐related diseases. In this study, zinc oxide nanoparticles (ZNPs) are utilized to evaluate NM‐induced autophagy and debate the mechanisms involved. It is found that ZNPs undergo pH‐dependent ion shedding and that intracellular zinc ions (Zn2+) play a crucial role in autophagy. Autophagy is activated with ZNPs treatment, which is inhibited after Zn2+ sequestration via ethylenediamine tetra‐acetic acid. Lysosome‐based autophagic degradation is halted after ZNPs treatment for more than 3 h and is accompanied by blockage of lysophagy, which renews impaired lysosomes. Furthermore, the microtubule (MT) system participates in ZNP‐induced lysosome–autophagy system changes, especially in the fusion between autophagosomes and lysosomes. MT acetylation is helpful for protecting from ZNP‐induced MT disruption, and it promotes the autophagic degradation process. In conclusion, this study provides valuable information on NM‐induced lysosome–autophagy system changes, particularly with respect to the role of lysophagy and the MT system, which point to some attractive targets for the design of engineered nanoparticles.