video: This animation explains the intracellular pathway and fate of anticancer drugs (oxaliplatin) and polymeric micelles (DACHPt-loaded micelle) in cancer cells after accumulation in solid tumors. The anticancer drug passes through the cellular membrane via passive diffusion or transporter, and moves to the cytoplasm. Then, the anticancer drug could be inactivated by defense proteins such as metallothionein. This mechanism is activated in the drug-resistant cancer cells. Consequently, the anticancer drug cannot reach the nucleus, where the target genome DNA exits. In contrast, polymeric micelles taken up by the cells thought the endocytosis. Polymeric micelles are stable until they reach the late endosome/lysosome, which resides close to the nucleus. Thus, polymeric micelles can bypass drug inactivation by defense proteins. In the late endosome/lysosome, polymeric micelles dissociated and released the active drug responding to specific proton and chloride ion concentrations. Thus, polymeric micelles efficiently deliver the active drug to the nucleus, achieving efficient cell death. In this way, polymeric micelles can overcome the drug resistance. This video relates to an article that appeared in the Jan. 5, 2011, issue of Science Translational Medicine, published by AAAS. The study, by Mami Murakami of the University of Tokyo in Tokyo, Japan, and colleagues was titled, "Improving Drug Potency and Efficacy by Nanocarrier-Mediated Subcellular Targeting." view more
Credit: [Video file © <i>Science</i>/AAAS]