Hepatocyte cytotoxicity evaluation with zinc oxide nanoparticles.

Our innate immunity is composed of several integral leukocytes including neutrophil, NK cell, macrophage or so. They are usually known to produce reactive oxygen species (ROS), in order to induce cell damages by these oxidizing reagents, and finally disrupting mitochondrial membrane to release cytochrome c. It is quite interesting to cancer therapy that the overexpressed cytochrome c level by ROS can lead to cancer cell death. Activated neutrophils exert anti-tumor effects against several carcinomas such as human skin melanoma by the increased production of ROS. To mimic the natural killing system, several nanoparticulates which contain cytotoxic properties have been in demand. Representatively, zinc oxide (ZnO) nanoparticles have been reported to have anti-bacterial and anti-cancer activity against various cancer cell lines due to production of ROS. They are shown to have preferential anti-cancer activity possibly due to higher level of oxidants and ROS in cancer cells. Inspired by these studies, we carried out the cytotoxicity evaluation of ZnO nanoparticulates against hepatocellular carcinoma. Our investigations were conducted by (1) screening the best size of ZnO (among 5, 50, and 100 nm) and the optimized time for anti-cancer effect against HepG2 cell line, (2) determining the apoptosis in the cells, and (3) regulating the production of intracellular ROS by ZnO nanoparticles. The ZnO nanoparticles revealed the dose-dependent toxic effect on HepG2 cells, irrespective of the sizes.