Polypeptides with brush-like architecture are emerging as ideal candidates for nanomedicine due to their unique physiochemical properties as well as excellent biological functions. To date, polypeptide brushes have been achieved by various living polymerization methods such as ring-opening metathesis polymerization (ROMP) and reversible deactivation radical polymerization (RDRP). However, several issues including cytotoxicity stemming from residual metal catalysts and peptide degradation at high polymerization temperature still remain. In this contribution, we present a benign and metal-free approach towards polypeptide brushes by photoinduced reversible-deactivation radical polymerization (photoRDRP), giving rise to a library of functional polypeptides with well-defined architecture (i.e., statistic and block), predetermined molecular weights, and low polydispersity. Two general classes of functional polypeptides including enzyme-responsive polypeptides and pro-apoptotic polypeptide brushes were accessed via photoRDRP, indicating its versatility in polypeptide synthesis. In the case of enzyme-responsive polypeptides (with pendent GPLGLAGG sequence), self-assembled spherical micellar nanoparticles exhibited shape-transformability through morphological metamorphosis into worm-like micelles upon enzyme-triggered cleavage of coronal peptide side chains. Moreover, pro-apoptotic KLA based polypeptides containing pendent (KLAKLAK)<sub>2</sub> side chains exhibited not only enhanced cell-penetrating activity but also increased cytotoxicity to cancer cells in comparison with free KLA peptide. Importantly, in vitro cell study showed that packing density of KLA side chains plays a crucial role in dictating the cytotoxicity of polypeptides. Those results clearly indicate the robustness of photoRDRP method in engineering the structure and properties of polypeptides, highlighting its immense potential in nanotechnology and biomedical applications.

Photoinduced reversible-deactivation radical polymerization (photoRDRP): Shedding light on structure and function of protein-like polymers

2019 Spring National Meeting

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