Proapoptotic Peptide Brush Polymer Nanoparticles via Photoinitiated Polymerization-Induced Self-Assembly

Hao Sun, Wei Cao, Nanzhi Zang, Tristan D. Clemons, Georg M. Scheutz, Ziying Hu, Matthew P. Thompson, Yifei Liang, Maria Vratsanos, Xuhao Zhou, Wonmin Choi, Brent S. Sumerlin, Samuel I. Stupp, Nathan C. Gianneschi*

*Corresponding author for this work

Research output: Contribution to journalArticlepeer-review

45 Scopus citations


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.

Original languageEnglish (US)
Pages (from-to)19136-19142
Number of pages7
JournalAngewandte Chemie - International Edition
Issue number43
StatePublished - Oct 19 2020


  • nanoparticles
  • peptide delivery
  • peptide–polymer conjugates
  • polymerization
  • scaled synthesis

ASJC Scopus subject areas

  • General Chemistry
  • Catalysis


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