PEG−Polypeptide Block Copolymers as pH-Responsive Endosome- Solubilizing Drug Nanocarriers
| Author(s) | Quadir, Mohiuddin A. | |
| Author(s) | Morton, Stephen W. | |
| Author(s) | Deng, Zhou J. | |
| Author(s) | Shopsowitz, Kevin E. | |
| Author(s) | Murphy, Ryan P. | |
| Author(s) | Epps, Thomas H. III | |
| Author(s) | Hammond, Paula T. | |
| Ordered Author | Mohiuddin A. Quadir, Stephen W. Morton, Zhou J. Deng, Kevin E. Shopsowitz, Ryan P. Murphy, Thomas H. Epps, III, and Paula T. Hammond | |
| UD Author | Murphy, Ryan P. | en_US |
| UD Author | Epps, Thomas H. III | en_US |
| Date Accessioned | 2015-12-16T19:24:57Z | |
| Date Available | 2015-12-16T19:24:57Z | |
| Copyright Date | Copyright © 2014 American Chemical Society | en_US |
| Publication Date | 2014-05-12 | |
| Description | Publisher's PDF. | en_US |
| 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. | en_US |
| Department | University of Delaware. Department of Chemical & Biomolecular Engineering. | en_US |
| Citation | PEG–Polypeptide Block Copolymers as pH-Responsive Endosome-Solubilizing Drug Nanocarriers. - Mol Pharmaceutics. (- 7):- 2420. | en_US |
| DOI | doi:10.1021/mp500162w | en_US |
| ISSN | 1543-8384 ; e-1543-8392 | en_US |
| URL | http://udspace.udel.edu/handle/19716/17323 | |
| Language | en_US | en_US |
| Publisher | American Chemical Society | en_US |
| dc.rights | ACS 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. | en_US |
| dc.source | Molecular Pharmaceutics | en_US |
| dc.source.uri | http://pubs.acs.org/journal/mpohbp | en_US |
| Title | PEG−Polypeptide Block Copolymers as pH-Responsive Endosome- Solubilizing Drug Nanocarriers | en_US |
| Type | Article | en_US |