【摘要】 通过两步ATRP制备了两亲性p H响应性超支化星形共聚物HP(DMAESP-co-BS2MOE)-(POEGMA)n.首先,以2-(2’-溴异丙酰氧基)乙基2″-甲基丙烯酰氧基乙基二硫化物(BS2MOE)为自引发单体,与甲基丙烯酰氧基-3-硫代己酸二甲氨基乙酯(DMAESP)共聚,得到超支化共聚物HP(DMAESP-coBS2MOE).然后以HP(DMAESP-co-BS2MOE)作为大分子引发剂引发甲基丙烯酸寡聚乙二醇酯(OEGMA)的聚合,得到超支化星形共聚物HP(DMAESP-co-BS2MOE)(POEGMA)n.在DMAESP中,叔胺基团和甲基丙烯酸酯基团通过酸敏感的β-硫丙酯键连接,由于该键在酸性条件下能够缓慢水解,形成羧基末端,最终得到的聚合物具有p H响应性.同时,由于BS2MOE中含有二硫键,能够被细胞中的谷胱甘肽还原,该聚合物同时具有氧化还原响应性.HP(DMAESP-co-BS2MOE)(POEGMA)n在水中能够自组装成以HP(DMAESP-co-BS2MOE)为核,以POEGMA为壳的纳米级胶束,并能负载DNA,可作为基因转染的载体.更多还原

【Abstract】 The p H-responsive hyperbranched star copolymers HP( DMAESP-co-BS2MOE)( POEGMA)ns have been successfully synthesized via two-step atom transfer radical polymerization( ATRP). The first step is polymerization of methacryloyloxy-3-thiahexanoyl-N,N-dimethyl acetate( DMAESP) and 2-( 2’-bromoisobutyryloxy) ethyl 2″-methacryloyl oxyethyl disulfide( BS2MOE). GPC analysis of HP( DMAESP-coBS2MOE) had a relatively wide molecular weight distribution and showed a double peak,which is consistent with the feature of hyperbranched polymers prepared by self-condensing vinyl polymerization. The resultant HP( DMAESP-co-BS2MOE) was used as macroinitiator in the subsequent ATRP of oligo( ethylene glycol)methacrylate( OEGMA). The molecular weights of the resultant hyperbranched star polymers apparently increased in comparison with HP( DMAESP-co-BS2MOE),but the polydispersity indexes decreased with the increase of polymerization time. In DMAESP,the methacrylate unit and tertiary amine group is linked by an acid-labile β-thiopropionate linker,which can be slowly degraded under mild acidic conditions( p H = 5. 0) to form carboxylic acid terminals,thus the HP( DMAESP-co-BS2MOE)( POEGMA)ns exhibit p H-responsive charge conversion behavior,which is highly favored in gene delivery application. Hyperbranched star copolymers containing disulfide bonds can be further degraded in the presence of glutathione in cytosol. When the hyperbranched star copolymers are self-assembled in water,micelles with the HP( DMAESP-co-BS2MOE)core and the POEGMA shell are formed. Transmission electron microscopy images showed formation of the spherical micelles. The average diameters of the micelles measured by DLS are in the range of 138 to 226 nm,after treated with 10 mmol / L DTT for 24 h,their diameters changed to 21 to 32 nm,and their molecular weights also significantly decreased. The experiments in vitro were performed on Hep G2 cells,the micelles formed by HP( DMAESP-co-BS2MOE)( POEGMA)nshowed relatively low cytotoxicity comparing to PEI 25 K and high DNA loading efficiency. After the internalization of as prepared polyplex,and the charge of the micelles was conversed to negative poly-ion,the efficient release of the loaded DNA was observed,and the micelles can be cleaved by GSH at the same time to further reduce the cyto-toxicity. Therefore,this system shows promising future as gene delivery application.更多还原