靶向激活型香豆素光扳机修饰的生物高分子光控释放体系的设计与研究

项目名称： 靶向激活型香豆素光扳机修饰的生物高分子光控释放体系的设计与研究

项目编号： No.51273064

项目类型： 面上项目

立项/批准年度： 2013

项目学科： 一般工业技术

项目作者： 包春燕

作者单位： 华东理工大学

项目金额： 80万元

中文摘要： 在常用的光扳机中，高的光剪切效率意味着使用前更严格的避光操作以防止不必要的光解发生，那么可否为光扳机加上"保险"，使其只有在特定的情况下才会被激活并发生光剪切呢？本项目以此为出发点设计了香豆素类靶向激活型光扳机：一方面通过在长波长单光子/近红外激光双光子可激发的7-氨基香豆素光扳机上引入分散红和硝基咪唑类淬灭因子来实现其"保险"功能；另一方面根据肿瘤细胞内GSH（谷胱甘肽）含量高、乏氧、pH值低等特性，分别引入二硫键、硝基咪唑、缩酮等三种肿瘤靶向激活因子来实现其"靶向激活"功能。最后，将这类连续可控的光扳机作为一类新的平台与生物相容的高分子载体（如壳聚糖）键联，从而高效地构建靶向激活-光激发连续控制的光控药物释放/基因转载体系，研究该类体系在药物输送/靶向/控释/癌症疾病治疗等方面的应用，为构建高选择性、高时空可控的光控释放体系提供一种新的思路和尝试。

中文关键词： 光扳机；靶向激活；香豆素；光控释放；壳聚糖

英文摘要： For common phototriggers, the higher photocleavage efficiency suffers from stricter dark operation before use to prevent the undesired photolysis. So, can we add "insurance" on them and make them just be activated under specific conditions to recover the photocleavage function? Based on this point, coumarin-based target-activated phototriggers are designed in this project: On the one hand, disperse red and nitromidazole groups are selected as the quenching factors ("insurance") into the framework of 7-amino coumarin phototrigger that can be excited either by one-photon long wavelength light or two-photon NIR laser to realize the "insurance" function; On the other hand, three kinds of tumor target-activated factors including disulfide, nitromidazole and ketal groups are introduced to realize the "target-activation" function according to the characters of the higher GSH concentration, hypoxia, and low pH value in tumor cells. Finally, the continuously controllable phototriggers are used as a new platform to chemically conjugate with biocompatible polymer carriers (like chitosan) to efficiently construct photo-controlled drug release/gene transfection systems with targeted activation-light excitation continuous controllability. And the applications for these photo-controlled release systems are further studied incl

英文关键词： Phototrigger；target-activation；coumarin；photo-release；chitosan