Epigallocatechin gallate-zinc oxide co-crystalline nanoparticles as an anticancer drug that is non-toxic to normal cells†
Decreased uptake and cellular accumulation of zinc is a common characteristic in cancer of the liver, pancreas and prostate, because these malignant cells are intolerant to the physiological concentrations of zinc. A tea polyphenol, epigallocatechin-3-gallate (EGCG), can enhance the cytotoxicity of zinc ions to cancer, but the application of this is limited by the low stability of EGCG. In this work, we have prepared a material that can simultaneously preserve the EGCG stability and facilitate zinc uptake and accumulation in cancer cells, under conditions that are not harmful to normal cells. Thus, we co-crystallize zinc oxide with EGCG to obtain hybrid EGCG-ZnO crystalline nanoparticles of 16.5 ± 5.3 nm in diameter. The EGCG-ZnO particles effectively kill PC-3 prostate adenocarcinoma cells at concentrations that are not cytotoxic to normal cells, WI-38 human embryonic lung fibroblasts. The EGCG-ZnO particles are two times more cytotoxic against PC-3 cells than the standard ZnO particles. In PC-3 cells, the EGCG-ZnO particles are taken up by endocytosis, followed by lysosomal disruption to release zinc and EGCG into the cytoplasm, finally resulting in nuclear accumulation of zinc.