Unknown

Dataset Information

0

PEG-polypeptide block copolymers as pH-responsive endosome-solubilizing drug nanocarriers.


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-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.

SUBMITTER: Quadir MA 

PROVIDER: S-EPMC4096223 | biostudies-literature | 2014 Jul

REPOSITORIES: biostudies-literature

altmetric image

Publications

PEG-polypeptide block copolymers as pH-responsive endosome-solubilizing drug nanocarriers.

Quadir Mohiuddin A MA   Morton Stephen W SW   Deng Zhou J ZJ   Shopsowitz Kevin E KE   Murphy Ryan P RP   Epps Thomas H TH   Hammond Paula T PT  

Molecular pharmaceutics 20140612 7


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  ...[more]

Similar Datasets

| S-EPMC9387087 | biostudies-literature
| S-EPMC3804265 | biostudies-literature
| S-EPMC5459121 | biostudies-other
| S-EPMC6473676 | biostudies-other
| S-EPMC7076537 | biostudies-literature
| S-EPMC6187445 | biostudies-literature
| S-EPMC4440445 | biostudies-literature
| S-EPMC6461212 | biostudies-literature
| S-EPMC6835295 | biostudies-literature
| S-EPMC11008427 | biostudies-literature