Proapoptotic Peptide Brush Polymer Nanoparticles via Photoinitiated Polymerization‐Induced Self‐Assembly
Abstract
Herein, we report the photoinitiated polymerization‐induced self‐assembly (photo‐PISA) of spherical micelles consisting of proapoptotic peptide–polymer amphiphiles. The one‐pot synthetic approach yielded micellar nanoparticles at high concentrations and at scale (150 mg mL−1) with tunable peptide loadings up to 48 wt. %. The size of the micellar nanoparticles was tuned by varying the lengths of hydrophobic and hydrophilic building blocks. Critically, the peptide‐functionalized nanoparticles imbued the proapoptotic “KLA” peptides (amino acid sequence: KLAKLAKKLAKLAK) with two key properties otherwise not inherent to the sequence: 1) proteolytic resistance compared to the oligopeptide alone; 2) significantly enhanced cell uptake by multivalent display of KLA peptide brushes. The result was demonstrated improved apoptosis efficiency in HeLa cells. These results highlight the potential of photo‐PISA in the large‐scale synthesis of functional, proteolytically resistant peptide–polymer conjugates for intracellular delivery.
Document Details
- Document Type
- Pub Defense Publication
- Publication Date
- Aug 26, 2020
- Source ID
- 10.1002/anie.202006385
Entities
People
- Brent Sumerlin
- Georg M. Scheutz
- Hao Sun
- Maria A. Vratsanos
- Matthew P. Thompson
- Nanzhi Zang
- Nathan C. Gianneschi
- Samuel I. Stupp
- Tristan D Clemons
- Wei Cao
- Wonmin Choi
- Xuhao Zhou
- Yifei Liang
- Ziying Hu
Organizations
- Air Force Office of Scientific Research
- National Heart, Lung, and Blood Institute
- National Science Foundation
- Northwestern University