期刊
ANGEWANDTE CHEMIE-INTERNATIONAL EDITION
卷 58, 期 48, 页码 17359-17364出版社
WILEY-V C H VERLAG GMBH
DOI: 10.1002/anie.201908634
关键词
biomaterials; nanomaterials; peptide brush polymer; photochemistry; polymerization
资金
- NIH through the NHLBI [R01HL139001]
- National Science Foundation [DMR-1710105]
- AFOSR MURI [FA9550-16-1-0150]
- Swiss National Science Foundation (SNSF)
Harnessing metal-free photoinduced reversible-deactivation radical polymerization (photo-RDRP) in organic and aqueous phases, we report a synthetic approach to enzyme-responsive and pro-apoptotic peptide brush polymers. Thermolysin-responsive peptide-based polymeric amphiphiles assembled into spherical micellar nanoparticles that undergo a morphology transition to worm-like micelles upon enzyme-triggered cleavage of coronal peptide sidechains. Moreover, pro-apoptotic polypeptide brushes show enhanced cell uptake over individual peptide chains of the same sequence, resulting in a significant increase in cytotoxicity to cancer cells. Critically, increased grafting density of pro-apoptotic peptides on brush polymers correlates with increased uptake efficiency and concurrently, cytotoxicity. The mild synthetic conditions afforded by photo-RDRP, make it possible to access well-defined peptide-based polymer bioconjugate structures with tunable bioactivity.
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