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Proapoptotic Peptide Brush Polymer Nanoparticles via Photoinitiated Polymerization‐Induced Self‐Assembly
Author(s) -
Sun Hao,
Cao Wei,
Zang Nanzhi,
Clemons Tristan D.,
Scheutz Georg M.,
Hu Ziying,
Thompson Matthew P.,
Liang Yifei,
Vratsanos Maria,
Zhou Xuhao,
Choi Wonmin,
Sumerlin Brent S.,
Stupp Samuel I.,
Gianneschi Nathan C.
Publication year - 2020
Publication title -
angewandte chemie international edition
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 5.831
H-Index - 550
eISSN - 1521-3773
pISSN - 1433-7851
DOI - 10.1002/anie.202006385
Subject(s) - peptide , micelle , polymerization , nanoparticle , polymer brush , polymer , hela , oligopeptide , biophysics , peptide sequence , copolymer , amphiphile , chemistry , materials science , nanotechnology , biochemistry , cell , organic chemistry , aqueous solution , biology , gene
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.