Stable azlactone-functionalized nanoparticles prepared from thermoresponsive copolymers synthesized by RAFT polymerization

A new class of stable azlactone-functionalized thermoresponsive nanoparticles have been synthesized and characterized. Such particles are based on well-defined copolymers of poly(N-isopropylacrylamide) (PNIPAM), poly(N,N-dimethylacrylamide) (PDMA) and poly(2-vinyl-4,4-dimethylazlactone) (PVDM) copolymers synthesized using reversible addition-fragmentation chain transfer (RAFT) polymerization. A well-defined PNIPAM macromolecular RAFT agent and a PDMA macromolecular RAFT agent of low polydispersities (PDIs = 1.04-1.12) were used to mediate the copolymerizations of DMA/VDM and of NIPAM/VDM, respectively, resulting in copolymers of M_n ranging from 19500 g mol^-1 to 64600 g mol^-1 and PDIs ranging from 1.04 to 1.20. Depending on the number-average polymerization degrees of NIPAM, DMA and VDM, lower critical solution temperatures (LCSTs) ranging from 36 °C to 44 °C were measured. Two block copolymers PNIPAM₄₆-b-P(VDM ₆-co-DMA₆₅) and PDMA₂₃-b-P(VDM ₁₀-co-NIPAM₄₆) have a LCST that occurs at the physiological temperature. Above the LCST, the resulting nanoparticles were covalently stabilized by reacting a diamine with azlactone rings. The size exclusion chromatography (SEC) analyses revealed that all unimers are incorporated into the core-crosslinked structures and into the shell-crosslinked structures. This new strategy of crosslinking nanoparticles based on thermoresponsive copolymers is of particular interest as it is highly efficient. The azlactone groups remaining in core-crosslinked nanoparticles are suitable to react with dansylhydrazine as shown by SEC analysis using UV detection.