Oxygen-tolerant photo-RAFT enables in-situ synthesis of protein-based nanoparticles

Protein-polymer conjugates are an important class of hybrid biomaterials with significant potential for biomedical applications. This study presents an innovative method for synthesizing and self-assembling these conjugates into nanoparticles using an oxygen-tolerant photoinitiated reversible addition-fragmentation chain transfer polymerization-induced self-assembly (RAFT-PISA) technique. By employing eosin Y/triethanolamine (EY/TEOA) as a photocatalyst system, oxygen inhibition is successfully overcome. As a model, a disulfide-containing bovine serum albumin (BSA) macro-RAFT agent is synthesized and used to control the copolymerization of N,N-dimethyl acrylamide (DMA) and diacetone acrylamide (DAAm). The resulting amphiphilic BSA-P(DMA-co-DAAm) conjugates self-assemble into well-defined spherical micelles. The study meticulously explores how various factors–such as the degree of polymerization (DP), DMA content, solid content, and grafting density (number of polymer chains per protein) affect the size and morphology of the nanoparticles. Finally, the introduction of reduction-sensitive disulfide linkages between proteins and synthetic polymers imparts degradability under biologically relevant redox conditions, making these conjugates promising candidates for drug delivery applications. This study offers a versatile and efficient strategy for the synthesis and self-assembly of protein-polymer conjugates into nanoparticles with potential applications in biomedicine.