A Transformable Chimeric Peptide for Cell Encapsulation to Overcome Multidrug Resistance

A Transformable Chimeric Peptide for Cell Encapsulation to Overcome Multidrug Resistance 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. http://www.deepdyve.com/assets/images/DeepDyve-Logo-lg.png Small Wiley

A Transformable Chimeric Peptide for Cell Encapsulation to Overcome Multidrug Resistance

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Publisher
Wiley
Copyright
© 2018 WILEY‐VCH Verlag GmbH & Co. KGaA, Weinheim
ISSN
1613-6810
eISSN
1613-6829
D.O.I.
10.1002/smll.201703321
Publisher site
See Article on Publisher Site

Abstract

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.

Journal

SmallWiley

Published: Jan 1, 2018

Keywords: ; ; ; ;

References

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