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 language | English |
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Pages (from-to) | 19136-19142 |
Number of pages | 7 |
Journal | Angewandte Chemie - International Edition |
Volume | 59 |
Issue number | 43 |
DOIs | |
Publication status | Published - Oct 19 2020 |
Keywords
- nanoparticles
- peptide delivery
- peptide–polymer conjugates
- polymerization
- scaled synthesis
ASJC Scopus subject areas
- Catalysis
- Chemistry(all)