Browsing by Author "Shopsowitz, Kevin E."
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Item PEG−Polypeptide Block Copolymers as pH-Responsive Endosome- Solubilizing Drug Nanocarriers(American Chemical Society, 2014-05-12) Quadir, Mohiuddin A.; Morton, Stephen W.; Deng, Zhou J.; Shopsowitz, Kevin E.; Murphy, Ryan P.; Epps, Thomas H. III; Hammond, Paula T.; Mohiuddin A. Quadir, Stephen W. Morton, Zhou J. Deng, Kevin E. Shopsowitz, Ryan P. Murphy, Thomas H. Epps, III, and Paula T. Hammond; Murphy, Ryan P.; Epps, Thomas H. IIIHerein 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-carboxyanhydridebased 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 selfassembly 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.