Facile preparation of nanomicelles using polymyxin E for enhanced antitumor effects

Abstract Chemotherapy is a major cancer treatment that uses antitumor drugs to kill fast-growing cancer cells. Many kinds of drug carriers have been developed to deliver and achieve controlled release of small-molecule therapeutic agents. However, many therapeutic agent carriers need complex preparation process. The natural polypeptides may serve as proper drug carriers. More specifically, polymyxin E (PE) is a kind of natural antibiotic lipopeptides. It is commonly used to treat infections caused by multidrug-resistant Gram-negative bacteria. Herein, we present a facile method to prepare DOX-loaded polymyxin E micelles (PE-DOX micelles) to enhance the therapeutic effect of anticancer drug doxorubicin (DOX). The hydrodynamic sizes and zeta potential of the prepared nanomedicine (PE-DOX micelles) were 142.0 nm and 6.47 mV, respectively. The release of DOX from PE-DOX micelles was faster at pH 5.5 than that at pH 7.4. Furthermore, PE exhibited negligible cytotoxicity to A549 cells and HeLa cells within 50 μg/mL, while PE-DOX micelles caused higher cytotoxicity than that of free DOX. Moreover, the intravenously injected PE-DOX micelles showed good biocompatibility and obvious antitumor effect after 14 days’ treatment in vivo. The PE-DOX micelles have great potential to be used as anticancer agent in the future. Graphical Abstract

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