Department: University of Delaware. Department of Chemical & Biomolecular Engineering.
Publisher: American Chemical Society
Date Issued: 2014-05-12
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-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.
