新型靶向输送-光控释放抗癌前药模型的设计合成及荧光成像研究

项目名称： 新型靶向输送-光控释放抗癌前药模型的设计合成及荧光成像研究

项目编号： No.21303120

项目类型： 青年科学基金项目

立项/批准年度： 2014

项目学科： 数理科学和化学

项目作者： 张有来

作者单位： 天津理工大学

项目金额： 25万元

中文摘要： 目前在癌症临床治疗的化疗过程中，因抗癌原药对癌细胞定向选择性差而导致的严重副作用，已成为制约癌症治疗效果的重要因素。为此，智能控制释放和原药靶向输送已成为新药研发中的两大热点。根据前期研究：1.独立研发的硫代色酮类光敏保护基具有既对光响应又能释放潜在荧光基团的特性，在光解离过程中释放的原药和荧光基团呈1：1的线性关系，在实现癌细胞荧光成像的同时可模拟生物体内药物释放，对于在生物细胞水平上开展药物定量释放研究和光控释药具有重要意义。2.叶酸作为原药的靶向载体具有无免疫性、性质稳定且无毒易得等特点。本课题首次探讨了具有双重定向功能的新型抗癌前药模型-即叶酸的靶向定位功能与光敏保护基的光控释药功能相结合。拟设计合成的新型抗癌原药模型集肿瘤靶向输送、光控释放、荧光药物积聚度成像三功能于一体，为抗癌新药研究提供实验依据和奠定理论基础，具有极大的挑战性、极强的理论意义和重大的应用价值。

中文关键词： 光敏保护基；硫代色酮；抗肿瘤；光控释药；荧光成像

英文摘要： The anticancer drugs which are used by now mostly have the disadvantage that they cannot be directionally transported to the cancer cells. There are serious side effects of chemotherapy for the treatment of cancer in the clinical treatment. They kill the cancer cells at the same time damnify the normal cells severely. Therefore, it is an important issue in medicine and pharmaceutics to develop new anticancer prodrugs, which are more active and specific in killing cancer cells. The new toxicity, high anti-cancer activity of new anticancer drugs have become the historic task and serious challenge to the field of biomedicine. There are two hot points of new anticancer drug development that are intelligent controlled drugs and targeted delivery. Based on my preliminary study, folic acid as the anticancer original drug targeting carrier has no immunity non-toxic and so on. This research is the first time that the use of folic acid cancer targeting positioning, combined with light controlled release characteristics of thiochromone derivatives photolabile protecting groups. On one hand, it is folic acid on cancer cells directed targeting. On the other hand, the photo-protective based directional light controlled release targeted delivery of anticancer drugs, in order to achieve the dual directional role. The novel ori

英文关键词： Photolabile protecting groups；Thiochromone；Anticancer；Photo-chtrolled release；Fluorescence imaging