Self-Assembling Peptide-Polymer Nano-Objects via Polymerization-Induced Self-Assembly

Self-assembling peptides (SAPs) have been extensively studied for their ability to form nanoscale ordered structures driven by noncovalent molecular interactions. Meanwhile, polymerization-induced self-assembly (PISA) has been exploited as a facile and efficient way to produce various amphiphilic block copolymer nano-objects, whose self-assembly was governed predominantly by the interactions of the different blocks with the polymerization medium. In this work, we combined PISA with SAPs to prepare novel peptide-polymer hybrid nano-objects, thus harnessing the advantages of PISA and the self-assembling driving force of SAPs. A tripeptide methacrylamide derivative (MAm-Gly-Phe-Phe-NH2, denoted as MAm-GFF, where MAm means methacrylamide) was copolymerized with glycerol monomethacrylate (GMA) to produce a P(GMA65-stat-(MAm-GFF)7) macro-chain transfer agent (macro-CTA) by reversible addition-fragmentation chain transfer polymerization in dimethylformamide. This peptide-based macro-CTA was then successfully chain-extended with poly(2-hydroxypropyl methacrylate) (PHPMA) by aqueous dispersion PISA, forming P(GMA65-stat-(MAm-GFF)7)-b-PHPMA28 self-assembled objects. Fibrous structures were observed by transmission electron microscopy (TEM) and Cryo-TEM, in agreement with depolarized dynamic light scattering, static light scattering, and small-angle X-ray scattering experiments that also revealed long anisotropic morphologies. Such structures have not been reported previously for PISA-prepared nano-objects. This confirms the decisive influence of the GFF SAP on the self-assembly. In addition, annealing the PISA suspension at different temperatures led to a significant size decrease in the self-assembled objects and to a morphological transition caused by the thermosensitivity of both the core-forming PHPMA block and the stabilizing P(GMA-stat-(MAm-GFF)) block.