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Bioactive Peptide Brush Polymers via Photoinduced Reversible‐Deactivation Radical Polymerization
Author(s) -
Sun Hao,
Choi Wonmin,
Zang Nanzhi,
Battistella Claudia,
Thompson Matthew P.,
Cao Wei,
Zhou Xuhao,
Forman Christopher,
Gianneschi Nathan C.
Publication year - 2019
Publication title -
angewandte chemie
Language(s) - English
Resource type - Journals
eISSN - 1521-3757
pISSN - 0044-8249
DOI - 10.1002/ange.201908634
Subject(s) - chemistry , thermolysin , peptide , bioconjugation , polymerization , macromonomer , polymer brush , polymer , radical polymerization , micelle , photochemistry , combinatorial chemistry , reversible addition−fragmentation chain transfer polymerization , amphiphile , cytotoxicity , aqueous solution , biophysics , organic chemistry , copolymer , trypsin , enzyme , biochemistry , biology , in vitro
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.