Multidrug resistance (MDR) remains one of the biggest obstacles in chemotherapy of tumor mainly due to P‐glycoprotein (P‐gp)‐mediated drug efflux. Here, a transformable chimeric peptide is designed to target and self‐assemble on cell membrane for encapsulating cells and overcoming tumor MDR. This chimeric peptide (C16‐K(TPE)‐GGGH‐GFLGK‐PEG8, denoted as CTGP) with cathepsin B‐responsive and cell membrane‐targeting abilities can self‐assemble into nanomicelles and further encapsulate the therapeutic agent doxorubicin (termed as CTGP@DOX). After the cleavage of the Gly‐Phe‐Leu‐Gly (GFLG) sequence by pericellular overexpressed cathepsin B, CTGP@DOX is dissociated and transformed from spherical nanoparticles to nanofibers due to the hydrophilic–hydrophobic conversion and hydrogen bonding interactions. Thus obtained nanofibers with cell membrane‐targeting 16‐carbon alkyl chains can adhere firmly to the cell membrane for cell encapsulation and restricting DOX efflux. In comparison to free DOX, 45‐time higher drug retention and 49‐fold greater anti‐MDR ability of CTGP@DOX to drug‐resistant MCF‐7R cells are achieved. This novel strategy to encapsulate cells and reverse tumor MDR via morphology transformation would open a new avenue towards chemotherapy of tumor.
Small – Wiley
Published: Jan 1, 2018
Keywords: ; ; ; ;
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