Biocompatible Single-Chain Polymeric Nanoparticles via Organo-Catalyzed Ring-Opening Polymerization

This study presents a novel approach to synthesize biocompatible single-chain polymeric nanoparticles (SCPN) under mild reaction conditions via organo-catalyzed ring-opening polymerization (ROP). Linear polymeric precursors containing pendent polymerizable caprolactone groups, made by reversible addition fragmentation chain transfer (RAFT) polymerization, were intramolecularly crosslinked via ROP in the presence of benzyl alcohol (nucleophilic initiator) and methanesulfonic acid (organ catalyst) to form discrete, well-defined SCPN, as confirmed by GPC, DLS, H-1 NMR, and AFM analysis. The formed SCPN are tunable in size (2-5 nm), depending on the molecular weight of the parent linear macromolecule. Furthermore, cytotoxicity studies revealed that the SCPN, which were covalently cross-linked by biodegradable polyester linkages, were nontoxic toward human embryonic kidney (HEK293T) cells. This study demonstrates the efficiency and versatility of this approach to generate uniformly sized soft nanoparticles with tunable dimensions that are potentially useful for a range of targeted applications, including drug delivery systems and membranes for gas separation technologies.