Radical Ring-Opening Polymerization-Induced Self-Assembly for the Synthesis of Degradable Particles Incorporating Ethyl Lipoate

Abstract

Polymeric nanoparticles are widely used in biomedical applications due to their ability to protect cargo, enhance bioavailability and enable controlled cargo release. Polymerization-induced self-assembly (PISA) is a versatile and scalable approach for nanoparticle preparation. However, the majority of PISA-derived systems lack degradability, which limits their potential for biomedical applications. Herein, we report a radical ring-opening polymerization-induced self-assembly (rROPISA) strategy to prepare redox-responsive degradable vinyl copolymer nanoparticles incorporating up to 30 mol% ethyl lipoate (LpEt). LpEt is the ethyl ester of the naturally occurring small molecule lipoic acid (LA), which can ring open to introduce reduction-labile disulfide-containing units along the polymer backbone. Well-defined nanoparticles with spherical, worm-like and pearl-necklace-like morphologies were readily obtained. The incorporation of disulfide linkages in the polymer chains was confirmed by reductive degradation of both copolymers and nanoparticles. The nanoparticles exhibited up to 75% loss in molecular weight upon treatment with 10 mM dithiothreitol (DTT) at 37 ºC. Cell viability study also confirmed the cytocompatibility of the polymeric particles, with all formulations demonstrating greater than 75% cell viability at solid contents up to 1.0 mg/mL. This strategy provides a versatile platform for the preparation of degradable, redox-responsive PISA nanoparticles, offering new opportunities for the design of stimuli-responsive polymeric nanomaterials for potential drug delivery applications.