项目名称： 癌细胞溶酶体靶向的纳米诊疗探针构建及其疗效自监测过程的可视化研究

项目编号： No.21505161

项目类型： 青年科学基金项目

立项/批准年度： 2016

项目学科： 数理科学和化学

项目作者： 田蒋为

作者单位： 中国药科大学

项目金额： 21万元

中文摘要： 针对癌症治疗过程中存在的靶点不明确、诊疗效率低、缺乏疗效监控等问题，本项目拟发展以癌细胞溶酶体为靶细胞器的纳米诊疗新策略：以生物相容的聚合物或氧化石墨烯为载体集成药物和荧光诊断探针，并通过叶酸表面功能化具备靶向识别癌细胞的功能；通过青蒿素介导的自由基效应、聚乙烯亚胺的质子海绵效应及氧化石墨烯的近红外光热效应三种方式破坏溶酶体，使组织蛋白酶以及药物从溶酶体释放而诱导癌细胞凋亡；借助荧光成像技术，通过pH激活荧光探针监测溶酶体膜的破裂以及原位检测细胞凋亡蛋白酶的激活实现疗效的可视化监测，从而建立一种药物靶向输送、动态示踪、药物治疗和疗效监测一体化的诊疗技术，为癌症早期诊断与治疗监控提供新方法，并推进纳米医学技术的发展。

中文关键词： 纳米探针；荧光探针；荧光成像；靶向治疗；可视化检测

英文摘要： Aiming at the problems of unclear target, low theranostic efficiency and lack of therapeutic monitoring in cancer treatment, this project plans to develop new cancer cell lysosome-targeted theranostic strategies: utilizing biocompatible polymer or graphene oxide to incorporate drug and fluorescence diagnostic probe to construct theranostics nanoprobes, and are functionalized with folate for target-cell-specific recognition. The nanoprobes destruct the lysosomes of cancer cells via artemisinin-mediated free radical effect, the proton sponge effect of poly(ethylene imine) or near-infrared photothermal effect of graphene oxide, leading to lysosomal escape of cathepsins and drug to induce the apoptosis of cancer cells. In virtue of fluorescence imaging, the therapeutic self-monitoring can be achieved through monitoring the rupture of lysosomal membrane by pH-activatable fluorescent probe or in situ detecting the activation of caspase. Therefore, this project proposes a theranostic technique with the integration of targeted drug delivery, dynamic tracking, therapy and therapeutic monitoring, which paves the way for early cancer diagnosis and treatment and promotes the development of nanomedicine.

英文关键词： nanoprobe ;fluorescent probe;fluorescence imaging;targeted therapy;visualized detection