Synthesis And Application Of Responsive Branched Star Copolymer And Block Copolymer

In the past decades,stimuli-responsive polymeric drug delivery systems have attracted great attention for cancer chemotherapy,owing to their specific structures and functionalities.Due to drawbacks of small chemotherapeutic drugs,the strategies have been explored by physically encapsulating small chemotherapeutic drugs into polymer matrix and polymeric assemblies to solve the problems.Camptothecin is an efficient anticancer drug and its fluorescence can be used to observe cellular uptake.However,both the released CPT and nanocarriers loading CPT showed a blue fluorescence,so it is hard to estimate whether the CPT is released from nanocarriers by observing the fluorescence.Polymerization-induced self-assembly and reorganization(PISR)is an efficient way to prepare nanomaterials,but using functional monomers in constructing core of nanomaterials and preparing stimuli-responsive nanomateirals through PISR still need further study.In this dissertation,we focus on the construction of functional nanomaterials for drug delivery.The primary results acquired are listed as follows:1.The photo-responsive camptothecin(CPT)prodrug monomer was designed.The amphiphilic branched star copolymer was synthesized through RAFT polymerization and CPT was covalently anchored onto the polymer backbone.The polymer was attached on the surface of silver nanoparticles(AgNPs)via the interaction between the disulfide of polymer and AgNPs.The fluorescence of CPT was quenched by AgNPs when their distance was close enough due to the overlap between absorbance range of AgNPs and emission wavelength of CPT.When CPT was attached on the surface of AgNPs,its fluorescence was quenched,and when CPT was released from AgNPs,the fluorescence recovered.Thus the intracellular drug release process and the distribution of CPT in cells could be traced by observing the fluorescence.2.The redox-responsive CPT prodrug monomer(CPTM)was synthesized.A series of polymeric prodrug nanomaterials were prepared via RAFT dispersion polymerization of CPTM using PHPMA as macro-RAFT agent.After being heated at 70 ? in ethanol,CPTM was slight soluble,however PCPTM was insoluble.As the degree of polymerization of CPTM gradually increased,polymeric nanomaterials were fabricated during the period of phase separation.Through changing the molar ratios of PHPMA/CPTM,nanomaterials with various morphologies could be prepared,including micelles,nanorods,nanowires,lamella and vesicles.In the reductive microenvironment of cancer cells,CPT could be released from nanomaterials and the drug loading content could be relatively high due to the core of nanomateirals constructed by PCPTM.