Bioactive Peptide Brush Polymers via Photoinduced Reversible‐Deactivation Radical Polymerization

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.

Document Details

Document Type
Pub Defense Publication
Publication Date
Oct 25, 2019
Source ID
10.1002/anie.201908634

Entities

People

  • Christopher J. Forman
  • Claudia Battistella
  • Hao Sun
  • Matthew P. Thompson
  • Nanzhi Zang
  • Nathan C. Gianneschi
  • Wei Cao
  • Wonmin Choi
  • Xuhao Zhou

Organizations

  • Army Research Office
  • National Institutes of Health
  • National Science Foundation
  • Northwestern University

Tags

Fields of Study

  • Chemistry

Readers

  • Molecular and Cellular Biochemistry
  • Nanocomposite Materials Science
  • Oncology (Cancer Research).

Technology Areas

  • Biotechnology
  • Biotechnology - Cancer Biotech