Study On Behavior And Properties Of Self-Assembly Induced By Ring Opening Polymerization Of Salicylic O-Anhydride Lactonate Monomer

Polymerization-induced self-assembly（PISA）is an effective method for preparing nanoassemblies of block copolymers.However,PISA using reversible addition-fragmentation chain transfer（RAFT）polymerization often has limitations such as low reaction activity and non-degradable polymers.In recent years,ring-opening polymerization-induced self-assembly（ROPISA）using N-carboxyanhydride（NCA）as a high-activity monomer has been used to synthesize biodegradable nanoparticles with high solid peptide content in a mild and efficient manner.However,there have been few studies on O-carboxyanhydride（OCA）,a similar high-activity monomer.A six-membered cyclic salicylic acid-based O-carboxyanhydride（SAOCA）monomer was successfully synthesized in-house,and simple nanoparticles were prepared using ROPISA.However,it is necessary to further explore the control of nanoparticle morphology and size under different reaction conditions,the underlying assembly mechanism,and the stability and controlled release effect of nanoparticles in different in vitro and in vivo environments,which has both theoretical and practical significance for the development and application of nanomaterials.This research mainly includes the following three parts:（1）Using the mild Lewis base 1,5,7-triazabicyclo[4.4.0]dec-5-ene（TBD）as a catalyst and flexible polyethylene glycol monomethyl ether(mPEG₁₁₃-OH,molecular weight 5 k Da)as an initiator,a system for catalyzing the ROPISA of SAOCA monomer was constructed.By adjusting the ratio of amphiphilic segments and monomer solid content,nanomicelles with various shapes such as spherical,worm-like,and donut-like were obtained.The polymer assembly process was studied by tracking the turbidity changes using UV spectrophotometry,analyzing the particle morphology evolution and assembly mechanism using transmission electron microscopy（TEM）.The results showed that high-activity SAOCA generated a large number of poorly soluble poly salicylic acid（PSA）fragments in a short time during polymerization,which remained in a non-equilibrium state and gradually stabilized with chain relaxation and motion after polymerization.The nanomorphology was jointly coordinated by concentration and the ratio of amphiphilic segments,with concentration being the dominant factor.Increasing the concentration enhanced the interaction force between aggregates and the assembly density between polymer molecules,making it easier to form worm-like nanoscale structures under high concentration conditions.（2）To investigate the stability and controllable drug release of the nanoparticles,we studied the environmental responsiveness and functional release of mPEG-PSA particles by simulating in vitro and in vivo microenvironments.UV monitoring showed that the release rate of salicylic acid（SA）from PSA decomposition was between 5%and 40%within 14 days,indicating that the nanoparticle had good environmental stability and potential as an auxiliary drug molecule.Negatively loaded Nile red（NR）nanoparticles were prepared using a cryo-embedding method,and the fluorescence test showed that the NR release rate was between 20%and 80%within 10 days,demonstrating the potential of the nanoparticles as drug carriers.（3）We expanded the polymerization of SAOCA monomer from two blocks to three blocks.After screening the co-monomers and catalytic systems,we found that using quinine ring（ABCO）as a catalyst and polyethylene glycol monomethyl ether(mPEG₄₅-OH,molecular weight of 2 k Da)as an initiator could induce the ring-opening polymerization reaction of phenylalanine O-carboxyanhydride（Phe OCA）and SAOCA,resulting in a highly regular mPEG-PPA-PSA triblock polymers.When the feed ratio of Phe OCA was 10 eq,SAOCA could achieve controllable chain growth in the range of 10 eq to 150 eq（M_n=5.32 k Da～24.60 k Da,D<1.35）.The triblock polymers have better controllability and tunability in the synthesis process,and its structure and properties can be controlled and adjusted by changing the reaction conditions.