Abstract
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.
| Original language | English (US) |
|---|---|
| Pages (from-to) | 17359-17364 |
| Number of pages | 6 |
| Journal | Angewandte Chemie - International Edition |
| Volume | 58 |
| Issue number | 48 |
| DOIs | |
| State | Published - Nov 25 2019 |
Funding
The authors are grateful for the support of the NIH through the NHLBI (R01HL139001), a National Science Foundation fund grant (DMR-1710105), and an AFOSR MURI (FA9550-16-1-0150). C.B. acknowledges the Swiss National Science Foundation (SNSF) for a postdoctoral fellowship.
Keywords
- biomaterials
- nanomaterials
- peptide brush polymer
- photochemistry
- polymerization
ASJC Scopus subject areas
- General Chemistry
- Catalysis
