pH/光双敏感含偶氮苯聚合物分子的设计及药物载体的应用  

Design and Drug Carrier Application of a Photo-Responsive and pH-Sensitive Azobenzene Polymer Molecule

作　　者：刘天奇[1] 雷彬[1] 徐首红[1] 刘洪来[1] LIU Tianqi;LEI Bin;XU Shouhong;LIU Honglai(Shanghai Engineering Research Center of Hierarchical Nanomaterials,School of Chemistry and Molecular Engineering,East China University of Science and Technology,Shanghai 200237,China)

机构地区：[1]华东理工大学上海多级结构纳米材料工程技术研究中心,化学与分子工程学院,上海200237

出　　处：《华东理工大学学报（自然科学版）》2021年第2期137-146,共10页Journal of East China University of Science and Technology

基　　金：国家自然科学基金(21776071);国家自然基金创新研究群体资助项目(51621002)。

摘　　要：采用原子转移自由基聚合(ATRP)法合成了一系列具有pH/光双敏感的两亲性嵌段聚合物C_(10)-偶氮苯(AZO)-C_(10)-聚甲基丙烯酸二异丙胺基乙酯(PDPA_(n))-聚乙二醇(PEG_(45))(n=30,50,80),用核磁、凝胶渗透色谱(GPC)对合成的聚合物进行表征,用动态光散射(DLS)测定聚合物自组装形成的胶束的粒径及电位,用紫外分光光度计测定聚合物的光敏感性以及聚合物胶束的pH敏感点,采用荧光分光光度计测定聚合物胶束的临界胶束浓度(CMC),模拟体外阿霉素释药。结果表明,合成的聚合物具有良好的pH敏感性和紫外可见光敏感性,并可以自组装得到粒径约为140~200 nm的均一、稳定的球状胶束,pH敏感点在6.3~7.2之间,并且在波长为365 nm和470 nm的两种光线下发生顺反结构的转变。选择pH敏感点在6.3左右的聚合物胶束运载抗癌药物阿霉素,后续体外释药实验表明聚合物胶束在pH或光刺激下可以很好地实现可控性释药,同时利用细胞毒性实验验证了聚合物胶束具有很低的细胞毒性,该聚合物有望成为一种潜在的pH/光响应型靶向药物载体。A series of amphiphilic block copolymers C_(10)-AZO-C_(10)-PDPA_(n)-PEG_(45)(C_(10)-azobenzene-C_(10)-poly[2-(diisopropylamino)ethyl methacrylate]-polyethylene glycol)(n=30,50,80)were designed and synthesized to improve stimuli-responsibility of pH/photo dual-responsive drug delivery system.In this paper,we used three steps to synthesize the copolymers.The data of proton nuclear magnetic resonance spectroscopy(^(1)H-NMR)and gel permeation chromatography(GPC)showed that copolymers were successfully synthesized.The florescence intensity ratio(I373/I384)of copolymeric micelles indicated that CMC(critical micelles concentrations)was negative correlation with PDPA polymerization degree.The image of transmission electron microscope showed that the copolymers were self-assembled to obtain uniform stable spherical micelle with particle size of 140—200 nm(0.3 mg/mL).Dynamic light scattering measurements were used to determine the diameters and Zeta potentials of the selfassembled copolymer micelles.Results showed that the copolymeric micelles were well dispersed in water.The structure of micelles was sensitively correlation with pH change.The pH-triggering points of copolymers were in the range of 6.3—7.2.And then,the reversible photo responsibility was investigated via UV-visible spectrophotometer.It was found that the absorption value of each copolymer micelle solution decreased at 350 nm(characteristic absorption peak of trans-AZO)and increased slightly at 440 nm(characteristic absorption peak of cis-AZO)when they were irradiated with 365 nm ultraviolet light,which indicated that the trans-structure was changed into cis-structure.After the solutions were irradiated with visible light of 470 nm,the cis-structures were found to convert into trans-structures again.Herein,we chose C_(10)-AZO-C_(10)-PDPA_(30)-PEG_(45)for further experiment as its pHtriggering points fitted the pH environment of normal and cancer cells.In vitro release kinetics of copolymer micelles were studied using fluorescence spectrophotometer under

关 键 词：pH/光双重响应 共聚物胶束 药物载体 细胞毒性 可控释放 

分 类 号：O69[理学—化学]