Quadir, Mohiuddin A.Morton, Stephen W.Deng, Zhou J.Shopsowitz, Kevin E.Murphy, Ryan P.Epps, Thomas H. IIIHammond, Paula T.2015-12-162015-12-16Copyright2014-05-12PEG–Polypeptide Block Copolymers as pH-Responsive Endosome-Solubilizing Drug Nanocarriers. - Mol Pharmaceutics. (- 7):- 2420.1543-8384 ; e-1543-8392http://udspace.udel.edu/handle/19716/17323Publisher's PDF.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-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.en-USACS AuthorChoice - This is an open access article published under an ACS AuthorChoice License, which permits copying and redistribution of the article or any adaptations for non-commercial purposes.Articledoi:10.1021/mp500162w