Orthogonal one-pot synthesis of multifunctional polypept(o)ide-based core-shell cylindrical polymer brushes

Abstract

Multi-functional core-shell cylindrical polymer brushes (CPBs) based on polypept(o)ides present an attractive alternative to self-assembled nanoparticles, offering biodegradability and improved structural integrety and complex chemical control over nanoparticle morphology and function. Hence, these structures have been explored for delivery of chemotherapeutics and siRNA, demonstrating their utility as drug carriers. Nevertheless, the synthesis of multifunctional CPBs remains challenging, due to limited chemical compatibility of protecting groups and deprotection conditions, often compromising the chemical integrity of CPB structures. Hence, to address this limitation, we developed a modular and orthogonal sequential ring-opening polymerization (ROP) strategy, enabling the synthesis of well-defined CPBs with benzyl, amine, or carboxyl functionalities. Our results demonstrate that these CPBs possess excellent colloidal stability, tunable hydrodynamic properties, low cytotoxicity, and high biocompatibility, establishing them as robust and adaptable platforms for next-generation drug delivery.