Anticancer properties of ZnO-Curcumin nanocomposite against melanoma cancer and its genotoxicity profiling

Abstract

The biological properties of curcumin are not fully understood due to its insolubility in water and poor bioavailability. Hence, to increase the bioavailability of curcumin, in this work chitosan-coated ZnO nanoparticle was used as a nanocarrier to deliver curcumin to cells. The synthesized ZnO-curcumin nanocomposite (ZnCurNC) was found to be very stable with more aqueous solubility, drug loading, entrapment and drug release efficiencies. In the in vitro cell viability assay (MTT), ZnCurNC was found to be more biocompatibility towards normal (CHO–K1) cells with selectively toxic to melanoma cancer (B16F10 cells). It was observed that, the release of curcumin from ZnCurNC at the site of cancer cells may be due to the acidic pH of the tumor microenvironment. The cell death of cancer cells was also correlated with the results of ROS production and apoptosis. As more cellular uptake of nanoparticles was noticed inside the cancer cells that might have triggered the production of ROS finally the cells undergone apoptosis. This in vitro anticancer property of ZnCurNC was further confirmed with the results of in vivo antitumor studies which revealed that C57BL/6 mice carrying melanoma tumor treated with ZnCurNC (40 mg/kg) with seven alternate doses reduced the tumor volume significantly. Immunohistochemical assays TUNEL assay and Ki-67 staining also revealed that there was an occurrence of a higher number of apoptotic cells with a reduced number of dividing cells in the tumor. To use ZnCurNC as chemotherapeutic agent, safety profiles are essential. Hence, a detailed genotoxicity studies were carried out both in in vitro (CHO–K1 cells) and in vivo (Swiss albino mice, C57BL/6) which revealed that ZnCurNC is not a mitotoxic, clastogenic, or aneugenic in nature. So, based on these detailed in vitro and in vivo biochemical studies, it is confirmed that ZnCurNC is biocompatible and can be a potential anticancer agent for the treatment of melanoma cancer.