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

Abstract

Herein, we report the photoinitiated polymerizationinduced self-assembly (photo-PISA) of spherical micelles consisting of proapoptotic peptide-polymer amphiphiles.T he one-pot synthetic approachy ielded micellar nanoparticles at high concentrations and at scale (150 mg mL À1)w ith 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.C ritically,t he 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 displayof KLA peptide brushes.T he result was demonstrated improved apoptosis efficiency in HeLa cells.T hese results highlight the potential of photo-PISA in the large-scale synthesis of functional, proteolytically resistant peptide-polymer conjugates for intracellular delivery.

Polymerization‐Induced Self‐Assembly: An Emerging Tool for Generating Polymer‐Based Biohybrid Nanostructures

“…Reproduced with permission. [ 118 ] Copyright 2020, Wiley‐VCH. C) Synthesis of peptide‐grafted block copolymer nanostructures via open‐to‐air ROMPISA, and composition of the BPC with hydrophilic block highlighted in blue and hydrophobic block illustrated in red.…”

(Bio)degradable and Biocompatible Nano-Objects from Polymerization-Induced and Crystallization-Driven Self-Assembly

“…Poly­( N , N -dimethylacrylamide) (PDMA) was another polyacrylamide that is often studied despite its less hydrophilic character than PAAm. Nanoparticles with a PDMA shell have shown interesting applications as ice-recrystallization inhibitors or for the synthesis of surface-functionalized materials. − For example, copolymerization of DMA and an acrylamide monomer functionalized with the proapoptotic peptide KLA (KLA­KLA­KLA­KLAK) was reported as a simple route toward peptide-based nanoparticles by PISA (Figure ). Chain extension by photo-PISA of the P­(DMA- co -KLAAm) macro-CTA with a mixture of DMA/DAAm in a buffer solution (pH = 5) gave stable spherical micelles with tunable sizes (36–105 nm in diameter) and high peptide loadings (up to 48 wt %).…”

“…Nanoparticles with a PDMA shell have shown interesting applications as ice-recrystallization inhibitors or for the synthesis of surface-functionalized materials. − For example, copolymerization of DMA and an acrylamide monomer functionalized with the proapoptotic peptide KLA (KLA­KLA­KLA­KLAK) was reported as a simple route toward peptide-based nanoparticles by PISA (Figure ). Chain extension by photo-PISA of the P­(DMA- co -KLAAm) macro-CTA with a mixture of DMA/DAAm in a buffer solution (pH = 5) gave stable spherical micelles with tunable sizes (36–105 nm in diameter) and high peptide loadings (up to 48 wt %). The enhanced proteolytic resistance of the peptide-functionalized nanoparticles was shown in comparison with the free KLA peptide in the presence of trypsin.…”

“…Schematic illustration of the one-pot photo-PISA approach to proapoptotic peptide brush polymer nanoparticles. Adapted from ref .…”

Constructing Cylindrical Nanostructures Via Directional Morphology Evolution Induced by Seeded Polymerization

“…In the past decade, polymerization‐induced self‐assembly (PISA) has been well established as an efficient and reliable strategy for scale‐up production of BCP nanoparticles with controllable size and morphology. [ 12–18 ] Although a few researchers have developed reliable PISA protocols for PCNs, [ 19–22 ] the preparation of PCNs through PISA of amorphous coil‐coil BCPs is still challenging. Recently, the self‐assembly behaviour of rod‐coil BCPs containing a crystalline/liquid‐crystalline (LC) rod block has been extensively investigated.…”