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Issue 6, 2020
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A self-assembled pH/enzyme dual-responsive prodrug with PEG deshielding for multidrug-resistant tumor therapy

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Abstract

Multidrug resistance (MDR) is one of the major obstacles for tumor therapy. Intake by receptor-mediated endocytosis enables molecules to bypass ABC transporter efflux, which is the primary mechanism of MDR. Here, we developed a novel pH/enzyme dual-responsive polypeptide prodrug to reverse multidrug resistance. This drug is composed of pH/MMP2-sensitive nanoparticles (MSNPs) self-assembled from mPEG–peptide–DOX. MSNPs can overcome sequential physiological barriers of multidrug resistance by prolonging the circulation time through PEGylation, enhancing tumor accumulation through passive targeting, increasing tumor penetration by enzyme-sensitive PEG deshielding, bypassing ABC transporter efflux by undergoing receptor-mediated endocytosis, and inducing sufficient DOX release from nanoparticles triggered by lysosomal pH. The reversal of MDR by MSNPs was evaluated in MCF-7/ADR cells and nude mice bearing tumors consisting of MCF-7/ADR cells. Both in vitro and in vivo studies showed that the MSNPs can effectively reverse MDR. Thus, MSNPs may constitute a potentially promising strategy for overcoming MDR in clinical applications.

Graphical abstract: A self-assembled pH/enzyme dual-responsive prodrug with PEG deshielding for multidrug-resistant tumor therapy

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Supplementary files

Article information


Submitted
14 Oct 2019
Accepted
27 Dec 2019
First published
22 Jan 2020

J. Mater. Chem. B, 2020,8, 1290-1301
Article type
Paper

A self-assembled pH/enzyme dual-responsive prodrug with PEG deshielding for multidrug-resistant tumor therapy

R. Ni, J. Zhu, Z. Xu and Y. Chen, J. Mater. Chem. B, 2020, 8, 1290
DOI: 10.1039/C9TB02264C

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