Thermally Induced Switch of Coupling Reaction Using the Morphological Change of a Thermoresponsive Polymer on a Reactive Heteroarmed Nanoparticle.

Control of the cross-linking reaction is imperative when developing a sophisticated in situ forming hydrogel in the body. In this study, a heteroarmed thermoresponsive (TR) nanoparticle was designed to investigate the mechanism of controlling reactivity of the functional groups introduced into the nanoparticles. The coupling reaction was suppressed/proceeded by utilizing temperature-induced morphological changes of the TR polymer. The heteroarmed TR nanoparticle was prepared by the coassembly of amphiphilic block copolymers possessing both a TR segment and hydrophilic segment with reactive functional groups of succinimide. The longer TR chain on the nanoparticle covered the succinimide group and suppressed the reaction with the primary amine on the external nanoparticle. In contrast, the coupling reaction was promoted at a high temperature to create the chemical cross-linking structure between the nanoparticles because of the exposure of the succinimide group on the surface of the particle as a consequence of the morphological change of the TR polymer. In addition, the thermally controlled chemical reaction modulated initiation of the gelation using a highly concentrated nanoparticle solution. The heteroarmed TR nanoparticle offers great practical advantages for clinical uses, such as embolization agents, through precise control of the reaction.