PEG–Polypeptide Block Copolymers as pH-Responsive Endosome-Solubilizing Drug Nanocarriers
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Quadir-2014-PEG-Polypeptide.pdf
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Author(s)
Morton, Stephen Winford
Deng, Zhou J.
Murphy, Ryan P.
Epps, Thomas H.
Quadir, Mohiuddin Abdul
Shopsowitz, Kevin
Hammond, Paula T
Date Issued
May 2014
Journal
Molecular Pharmaceutics
Publisher
American Chemical Society (ACS)
Citation
Quadir, Mohiuddin A., Stephen W. Morton, Zhou J. Deng, Kevin E. Shopsowitz, Ryan P. Murphy, Thomas H. Epps, and Paula T. Hammond. “PEG–Polypeptide Block Copolymers as pH-Responsive Endosome-Solubilizing Drug Nanocarriers.” Mol. Pharmaceutics 11, no. 7 (July 7, 2014): 2420–2430. © 2014 American Chemical Society
Version
Final published version
Abstract
Herein we report the potential of click chemistry-modified polypeptide-based block copolymers for the facile fabrication of pH-sensitive nanoscale drug delivery systems. PEG–polypeptide copolymers with pendant amine chains were synthesized by combining N-carboxyanhydride-based ring-opening polymerization with post-functionalization using azide–alkyne cycloaddition. The synthesized block copolymers contain a polypeptide block with amine-functional side groups and were found to self-assemble into stable polymersomes and disassemble in a pH-responsive manner under a range of biologically relevant conditions. The self-assembly of these block copolymers yields nanometer-scale vesicular structures that are able to encapsulate hydrophilic cytotoxic agents like doxorubicin at physiological pH but that fall apart spontaneously at endosomal pH levels after cellular uptake. When drug-encapsulated copolymer assemblies were delivered systemically, significant levels of tumor accumulation were achieved, with efficacy against the triple-negative breast cancer cell line, MDA-MB-468, and suppression of tumor growth in an in vivo mouse model.
MIT Department
Massachusetts Institute of Technology. Department of Chemical Engineering
Koch Institute for Integrative Cancer Research at MIT
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DOI of Published Version
https://doi.org/10.1021/mp500162w
