Abstract
Mitochondria-targeted and pH-triggered charge-convertible polymeric micelles (GPTD) were developed for doxorubicin (DOX) delivery and targeted anticancer therapy. GPTD surface was negatively charged under physiological pH (7.4), while it converted to positive charge under tumor pH (6.8). Sustained release of DOX from the drug loaded polymeric micelles was observed and the drug release was accelerated by decreasing the medium pH from 7.4 to 6.8. Cellular uptake by U251 glioma cells showed that GPTD can enhance the accumulation of polymeric micelles inside the mitochondria after charge-mediated cellular internalization and release DOX into the cellular interior. In vivo anticancer activity performed on glioma Balb/c nude mice demonstrated that the DOX-containing GPTD could remarkably inhibit the tumor growth, and displayed a significant reduction of tumor tissue cells and fewer Ki67 positive cells compared to the PBS group. Hence, this mitochondrial targeted and pH-triggered charge-convertible polymeric micellar system showed substantial promise for anticancer therapy.
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