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

Research output: Contribution to journalArticle

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.

Original languageEnglish
Pages (from-to)19136-19142
Number of pages7
JournalAngewandte Chemie - International Edition
Volume59
Issue number43
DOIs
Publication statusPublished - Oct 19 2020

Keywords

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

ASJC Scopus subject areas

  • Catalysis
  • Chemistry(all)

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  • Cite this

    Sun, H., Cao, W., Zang, N., Clemons, T. D., Scheutz, G. M., Hu, Z., Thompson, M. P., Liang, Y., Vratsanos, M., Zhou, X., Choi, W., Sumerlin, B. S., Stupp, S. I., & Gianneschi, N. C. (2020). Proapoptotic Peptide Brush Polymer Nanoparticles via Photoinitiated Polymerization-Induced Self-Assembly. Angewandte Chemie - International Edition, 59(43), 19136-19142. https://doi.org/10.1002/anie.202006385