Synthesis and properties of stimuli-sensitive heterografted toothbrush-like terpolymers with a linear handle and two types of V-shaped grafts

This study aims at synthesis and properties of multifunctional AB2mC2m-type toothbrush-like copolymers. The target copolymers comprising a relatively long linear PNIPAM block and a relatively short comb-like block with V-shaped (PAA)2 and (PCL)2 grafts were controllably synthesized by multistep reactions. DSC results revealed that various segments in copolymers were partly compatible. The high grafting density, structural diversity and/or crystalline nature of PCL segments allowed stimuli-induced versatile morphological transitions, and the terpolymer was liable to self-assemble into spherical micelles (25 °C), sea cucumber-like micelles (25 °C, pH 5.3), vesicles (37 °C), and spherical micelles and their aggregates (37 °C, pH 5.3) due to the change in inter- and intramolecular interactions. As compared with the copolymer aggregates formed from the linear analogue with a similar composition, toothbrush-like copolymer based aggregates were liable to exhibit reduced critical aggregation concentration, higher drug loading efficiency, faster release kinetics and enhanced storage stability, and they could act as more efficient vehicles for thermo, pH and additive (β-CD and GSH) triggered drug delivery. Upon a single stimulus or combined stimuli, doxorubicin-loaded aggregates exhibited significantly accelerated drug release kinetics. Our study affords a robust method to generate novel heterografted toothbrush-like copolymers, and the success of this research has important implications for exploring the unique properties and bioapplications of nonlinear multicomponent copolymers.