In Vitro And In Vivo Anti-melanoma Activity Of ZnO Nanoparticles

Melanoma is one of the most aggressive skin cancers.It easily metastasizes and has high mortality.Although a variety of clinical methods have been used for melanoma treatment,there are many limitations such as: easy relapse,drug resistance,side effects.The development of nanotechnology provides a new strategy for melanoma treatment.ZnO nanoparticles（ZnO NPs）are commonly used as antibacterial drugs due to their excellent biocompatibility,biodegradability and biofunctionality.Recent studies indicate that ZnO NPs exhibite selective toxicity to cancer cells whereas good biocompatibility to normal cells.ZnO NPs are expected to become antitumor materials for preventing recurrence after melanoma surgery.In this study,we prepared the spherical ZnO NPs with the particle size less than10 nm by a simple chemical method.In vitro cytotoxicity assay,a certain concentration range（20-35 μg/mL）of ZnO NPs showed cytotoxicity to B16F10 melanoma cells,while it barely affected the viability of 3T3L1 fibroblast cells.When cultured with B16F10 cells,ZnO NPs induced the generation of reactive oxygen and mitochondrial superoxide via releasing Zn²⁺,which led to oxidative stress in the cells and further reduced the mitochondrial membrane potential,decreased the number of mitochondrial cristae.Furthermore,damaged mitochondria induced the release of apoptosis factors to promote cell apoptosis.FITC-Annexin V/propidium iodide double staining assay was used to analyze different apoptosis stages of B16F10 cells induced by ZnO NPs.The results showed that ZnO NPs induced cell cycle arrest at the G2/M phase in B16F10 cells.A polymer hydrogel（Gel-F127-ZnO NPs）with F127 as a carrier was designed for evaluating the antimelanoma effect of ZnO NPs in vivo.The in vivo experiment indicated that the tumor recurrence was inhibited in tumor-bearing mice treated with Gel-F127-ZnO NPs.Conclusively,ZnO NPs showed strong antitumor effects both in vitro and in vivo.