The Preparation And Application Of Hyperbranched Polythioether

Hyperbranched polymer?HBP?owns dendritic ellipsoidal structure,abundant surface functional groups and large internal space,which were widely used in the field of nanocarriers,medical imaging and gene transfection.Hyperbranched polymers containing sulfur,phosphorus and selenium atoms have received extensive attention due to their special functionality.In this work,a series of hyperbranched polythioethers?HBPTE?with tunable backbone and terminal groups were prepared using thiol click chemistry via one-pot methodology,and thiol-terminated hyperbranched polythioethers were functionalized to explore its potential application in the field of unimolecular nanomedicine.The specific research contents are as follows:1)Using a diacrylate compound as the AA'monomer?where A represents methacrylate,A'represents acrylate?,and tris?3-mercaptopropionic acid?ester compound as B₃ monomer,a series of hyperbranched polythioethers with tunable backbone and thiol-terminated were prepared by selective thiol-ene click chemistry via one-pot methodology.Since the reactivity of the acrylate with thiol was much higher than that of the methacrylate,the AA'monomer and the B₃ monomer rapidly reacted to form an AB₂ type intermediate in initial stage of polymerization,and the intermediate further polymerized to obtain a thiol-terminated hyperbranched polythioethers.The polymerization process showed excellent selectivity without the gelation risk of traditional A₂+B₃ system,and hyperbranched polythioether prepared showed clear structure,high molecular weight and narrow molecular weight distribution.2)Using glycidyl methacrylate?GMA?as an AC monomer?where A represents methacrylate,C represents epoxy?,tris?3-mercaptopropionic acid?ester compound as B₃monomer,a series of hyperbranched polythioethers with tunable backbone and terminal groups were prepared by thiol-ene and thiol-epoxide click chemistry reaction via one-pot methodology.Since the reactivity of methacrylate with thiol is higher than that of epoxide under the condition of base catalysis,AC monomer may rapidly react with B₃ monomer to form CB₂ or BC₂ type intermediate depending on monomer molar ratio,and then the intermediate further polymerized to obtain hyperbranched polythioether with tunable terminal groups.When the molar ratio was 1:0.8¹.0,thiol-terminated hyperbranched polythioether could be obtained;when the molar ratio was 1:2.0².4,epoxide-terminated hyperbranched polythioether could be obtained.The polymerization showed excellent controllability without gelation.3)The amphiphilic hyperbranched star polymer?HBPTE-PEG?was prepared by functionalization of thiol-terminated hyperbranched polythioether via thiol-ene click chemistry.The amphiphilic hyperbranched star polymer formed unimolecular micelles with hyperbranched polythioether as hydrophobic core and polyethylene glycol?PEG?as hydrophilic shell in aqueous solution.Drugs?doxorubicin,camptothecin and cisplatin?were embedded or chemical linked into the amphiphilic hyperbranched star polymer.The nanomedicine chemical linked showed excellent stability,higher loading efficiency and stimuli-responsive release.Cytotoxicity measurements demonstrated that drug-loading micelles showed higher anti-cancer efficiency,while the hyperbranched star polymers showed cytotoxicity.Degradation experiments demonstrated that hyperbranched star polymers biodegradability.