Application Of Controlled Radical Polymerization In Synthesis Of Multi-Cyclic Polymers And Polymerization-Induced Self-Assembly

The area of polymer synthesis has got much development as the advent of controlled radical polymerization.As a result,various polymers with complex structures have been produced,including dentrimer,hyperbranched polymer,comb-shape polymer and cyclic polymer.Among these,cyclic polymer has received much attention due to its unique structure.In this dissertation,we successfully synthesized multi-cyclic polymers including bicyclic polymer and tetracyclic polymer through combining ATRP and high-efficient light-induced coupling reaction.Besides,controlled radical polymerization has promoted the development of polymerization-induced self-assembly(PISA)which has been a most powerful tool for preparing polymer nanoparticles.Meanwhile,polymer nanoparticles have been widely used in drug delivery system.In this dissertation,we prepared a core-crosslinked nanoparticle with pH-and reductive-responsive properties to study its performance in drug delivery.The primary results are presented as follows:1.Multicyclic polymers including bicyclic and tetracyclic polymers were constructed by combining atom transfer radical polymerization(ATRP)and photo-induced coupling reaction of anthryl groups.First,4-arm and 8-arm star polystyrenes were synthesized by ATRP using the tetrafunctional and octafunctional initiators,respectively.Subsequently,after two-step modification of Br-terminated 4-arm and 8-arm star polystyrenes,including azidation and copper-catalyzed azide-alkyne cycloaddition(CuAAC)reaction with prop-2-yn-l-yl anthracene-9-carboxylate,the presurcors with anthryl end groups were obtained.Finally,the photo-induced coupling reaction was conducted upon irradiation at 365 nm in the diluted solution of 4-arm and 8-arm star precursors,to produce bicyclic and tetracyclic polymers.Besides,the multicyclic polymers can convert back to the original precursors after heating at 150 0C.'H NMR?FT-IR?GPC and UV-vis analyses were carried out to verify the resultant multicyclic structures and topological conversion between multi-cyclic polystyrenes and their precursors.2.Core-crosslinked nanoparticle which consists of PEG-P(NBMA-co-DSDMA)was prepared by PISA using photo-responsive NBMA as monomer and reductive-responsive DSDMA as crosslink agent.After irradiation of the nanoparticle at 365 nm,the NBMA moieties were transformed to carboxyl groups,which caused the hydrophobic-to-hydrophilic transition of the core and made the nanoparticles become negative.Therefore,DOX·HCl with positive charge can be effectively encapsulated into nanoparticles(drug loading efficiency up to 82%).Drug release experiments indicated that 80%of DOX could be released within 24 h under mild acid environment(pH=5.4),with the existence of GSH.In vitro cytotoxicity assay showed this kind of nanoparticles without DOX exhibited negligible cytotoxicity even at concentration up to 1000 p^g/mL.In addition,this prodrug carrier had a rapid escape rate from endosome and effective intracellular drug delivery performance.So this core-crosslinked polymeric nanoparticles could be used as an efficient drug delivery system to achieve high anticancer therapy.