多肽修饰的还原敏感型靶向光敏剂的合成及生物活性评价  

Design, Synthesis and Biological Activity of R8-Modified Reduction-Sensitive Targeting Photosensitizer

作　　者：李鹏熙 刘忠洪 杨玲玲 杨兵 LI Peng-xi;LIU Zhong-hong;YANG Ling-ling;YANG Bing(School of Environmental and Quality Detection,Chongqing Chemical Industry Vocational College,Chongqing 401228,China;Department of Occupational Health,Third Military Medical University,Chongqing 400038,China)

机构地区：[1]重庆化工职业学院环境与质量检测学院,重庆401228 [2]第三军医大学军事预防医学院,重庆400038

出　　处：《西南师范大学学报（自然科学版）》2019年第7期23-29,共7页Journal of Southwest China Normal University(Natural Science Edition)

基　　金：重庆市基础与前沿研究计划项目(cstc2016jcyjA0075)

摘　　要：采用穿膜肽(八聚精氨酸)作为连接基团,双硫键为敏感化学键,叶酸作为靶向基团,修饰光敏剂替莫卟吩(m-THPC),制备了一种多肽修饰的还原敏感型靶向光敏剂1,其结构经核磁共振氢谱(1HNMR)和基质辅助激光离子化飞行时间型质谱仪(MALDI-TOF-MS)进行表征.研究表明,八聚精氨酸的引入,可显著改善m-THPC的溶解度和提高肿瘤细胞的靶向性;在谷光甘肽(GSH)作用下,光敏剂1可释放出m-THPC,6h时的释放率大于80%.细胞毒性实验表明,光敏剂1在浓度为15μmol/L时,HeLa细胞的存活率可降至36.1%,细胞毒性大于叶酸-PEG-羧酸卟吩(光敏剂7).The present study reported the preparation of a novel R8-modified redox-reponsive prodrug containing meso-tetra (m-hydroxy phenyl) chlorin (m-THPC),octaarginine(R8) and folate.The structure of target compound was characterized by UV-Vis,IR,HPLC,1HNMR,MS spectra.The results show that the introduction of octa-arginine can significantly improve the solubility of m-THPC and increase the targeting property for tumor cells.m-THPC can be released from photosensitizer 1 under the action of GSH,and the release rate was more than 80% at 6 h.The cytotoxicity test showed that the survival rate of HeLa cell can be reduced to 36.1% when the concentration of photosensitizer 1 is 15 μmol/L,and the cytotoxicity of photosensitizer 1 is stronger than photosensitizer 7.

关 键 词：八聚精氨酸 还原敏感型 叶酸靶向 光敏剂 生物活性 

分 类 号：O625.6[理学—有机化学]