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|a Morton, Stephen Winford
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|a Massachusetts Institute of Technology. Department of Chemical Engineering
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|a Koch Institute for Integrative Cancer Research at MIT
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|a Quadir, Mohiuddin Abdul
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|a Morton, Stephen Winford
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|a Deng, Zhou J.
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|a Shopsowitz, Kevin
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|a Hammond, Paula T.
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|a Deng, Zhou J.
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|a Murphy, Ryan P.
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|a Epps, Thomas H.
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|a Quadir, Mohiuddin Abdul
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|a Shopsowitz, Kevin
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|a Hammond, Paula T
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|a PEG-Polypeptide Block Copolymers as pH-Responsive Endosome-Solubilizing Drug Nanocarriers
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|b American Chemical Society (ACS),
|c 2015-06-22T15:14:00Z.
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|z Get fulltext
|u http://hdl.handle.net/1721.1/97496
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|a 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.
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|a Novartis Institutes of Biomedical Research
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|a National Institutes of Health (U.S.) (Centers for Cancer Nanotechnology Excellence Grant P30 CA14051)
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|a National Institutes of Health (U.S.) (Centers for Cancer Nanotechnology Excellence Grant 5 U54 CA151884-02)
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|a National Science Foundation (U.S.). Graduate Research Fellowship
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|a Natural Sciences and Engineering Research Council of Canada (Postdoctoral Fellowship)
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|a en_US
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|a Article
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|t Molecular Pharmaceutics
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