PEG−Polypeptide Block Copolymers as pH-Responsive Endosome- Solubilizing Drug Nanocarriers
Date
2014-05-12
Journal Title
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Publisher
American Chemical Society
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.
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Citation
PEG–Polypeptide Block Copolymers as pH-Responsive Endosome-Solubilizing Drug Nanocarriers. - Mol Pharmaceutics. (- 7):- 2420.