期刊
MOLECULAR PHARMACEUTICS
卷 11, 期 7, 页码 2420-2430出版社
AMER CHEMICAL SOC
DOI: 10.1021/mp500162w
关键词
block copolymer; nanocarriers; pH-responsive; drug delivery
资金
- Novartis Institutes for BioMedical Research, Inc.
- NIH
- Center for Cancer Nanotechnology Excellence (CCNE) [P30 CA14051, 5 U54 CA151884-02]
- Koch Institute for Integrative Cancer Research at MIT
- NSF
- NSERC
- National Institute of General Medical Sciences of the National Institutes of Health (NIH) [P20GM103541]
- Office Of The Director
- Office of Integrative Activities [1301765] Funding Source: National Science Foundation
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.
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