Synthesis And Characterization Of Advanced Topological Polymers As Drug Carriers

Polymeric micelles have attracted increasing attention during the past several decades.However,the stability of traditional micelles self-assembled from linear polymers remains a substantial challenge for their practical applications and clinical translations,because the occurrence of structural disassembly will result in premature drug release and severe side effects to the normal tissues.To enhance the micelle stability,various methods have been developed.Among these,introduction of advanced topology such as cyclic,star-shaped and hyperbranched structure into polymers has been repeated highlighted to be an effective means.Based on this,aiming at cyclic and hyperbranched polymers,we proposed novel synthetic routes of the cyclic block copolymers and tadpole-like amphiphilic block copolymers,and simplified the synthetic route of hyperbranched polymeric prodrug.The detailed works were listed as follows:1.We brought cyclic topology to the hydrophilic block of an amphiphilic block copolymer synthesizing a tadpole-like amphiphilic copolymer,(c-POEGMA)-b-PCL(C),which composed of a cyclic hydrophilic segment and a linear hydrophobic moiety.The self-assembled C micelles showed greater stability relative to the L analogues in terms of lower CMC,smaller particle size,slower in vitro drug release profile and less in vitro cytotoxicity against HeLa cells.This work thus reveals that the cyclic hydrophilic moiety can offer extra stability for the self-assembled micelles due to the topological structure-enhanced steric hindrance,which provides an alternative to fabricate polymeric micelles toward enhanced stability for in vivo applications.2.We synthesized a cyclic polymer,c-(PNIPAAm-b-POEGMA)combining reversible addition-fragmentation transfer(RAFT)polymerization,one-pot aminolysis/Michael addition reaction and intrachain Cu(I)-catalyzed azide-alkyne cycloaddition(CuAAc).The cyclic diblock copolymers exhibited signifiantly higher lower critical solution temparature(LCST)relative to the linear counterparts.More importantly,the spherical micelles self-assembled by the cyclic diblock copolymers showed smaller average size and narrower size distribution than the ones formed by the linear formulations.Overall,this study reported an alternative toward cyclic block copolymers as well as provided new insights into the structure-property relationship of cyclic polymers.3.We designed and synthesized an All-in-One chain transfer monomer(ACTM),integrates triple functions including a CTM structure for generation of HPs,a CPT molecule for simultaneous production of prodrugs and dual-responsive(acidic pH-sensitive carbonate group and reduction-responsive disulfide bond)for efficient intracellular polymer degradation and drug release.Then using this ACTM,we achieved one-pot preparation of dual-responsive hyperbranched polymeric prodrugs(DRHPPs).The resulting DRHPPs with precisely regulated drug loading content and great therapeutic efficacy offered a highly promising platform for efficient anticancer drug delivery.Therefore,we developed an extreme simplified method preparing the hyperbranched polymeric prodrug.