H-bond-type thermo-responsive schizophrenic copolymers: The phase transition correlation with their parent polymers and the improved protein co-assembly ability.

Schizophrenic copolymers are one type of the popular smart polymers that show invertible colloidal structures in response to temperature stimulus. However, the lack of principles to predict the phase transition temperature of a schizophrenic copolymer from its corresponding parent thermo-responsive polymers limits their development. Additionally, studies on their applications remain scarce. Herein, a series of schizophrenic copolymers were synthesized by polymerization of a RAFT-made polymer precursor poly(acrylamide-co-N-acryloxysuccinimide-co-acrylic acid) (P(AAm-co-NAS-co-AAc)) with the mixture of N-isopropylmethacrylamide (NIPAm) and acrylamide (AAm) in varying molar ratios. In aqueous solution, the block P(AAm-co-NAS-co-AAc) and the block poly(NIPAm-co-AAm) exhibited upper and lower critical solution temperature (UCST and LCST) behavior, respectively. The schizophrenic copolymers featured either UCST-LCST, LCST-UCST, or only LCST thermo-responsive transition. A preliminary correlation of phase transition between the schizophrenic copolymers and their parent polymers was summarized. Furthermore, the co-assembly of the schizophrenic copolymers and proteins were conducted and the kinetics of protein loading and protein activity were investigated, which showed that the schizophrenic copolymers were efficient platforms for protein co-assembly with ultra-high protein loading while preserving the protein bioactivities. Additionally, all the materials were non-toxic towards NIH 3T3 and MCF-7 cells. This work offers the prospects of the schizophrenic polymers in soft colloidal and assembly systems, particularly in guiding the design of new materials and their use in biomedical applications.