生物自发光触发高荧光碳量子点基复合光敏剂的合成及其光动力治疗性能研究

项目名称： 生物自发光触发高荧光碳量子点基复合光敏剂的合成及其光动力治疗性能研究

项目编号： No.51502345

项目类型： 青年科学基金项目

立项/批准年度： 2016

项目学科： 一般工业技术

项目作者： 李钒

作者单位： 中国人民解放军军事科学院军事医学研究院

项目金额： 21万元

中文摘要： 目前，光敏剂及其激发光源的组织穿透限制是影响光动力疗法（PDT）发展的关键。纳米载体传输是一种有效途径，碳量子点（CDs）优异的荧光性能、良好的生物相容性、表面易修饰等特点使其在PDT领域更具优势。而生物荧光可触发现有光敏剂，且可避免组织穿透障碍。因此，本项目拟结合前期工作基础，选择适宜的有机物与叶酸混合前躯体、含氮钝化剂以及镁盐，水热合成具有高荧光性能、表面叶酸修饰和氮-镁双杂化的CDs，剖析CDs的生长规律及荧光调控机制；在此基础上，将光敏剂二氢卟吩e6（Ce6）和海肾萤光素酶（Rluc8）通过化学偶联反应结合在CDs表面，形成生物自发光触发的复合光敏剂Rluc8-CDs-Ce6，分析Rluc8、CDs和Ce6之间荧光共振能量转移机制，探索Rluc8-CDs-Ce6对肿瘤细胞的荧光成像诊断与PDT效果。这种生物自发光触发的RLuc8-CDs-Ce6有望成为一种较理想的肿瘤PDT光敏剂。

中文关键词： 碳量子点；光动力疗法；生物自发光；光敏剂；肿瘤

英文摘要： The present imperfect photosensitizers and the limitation of light penetration in living tissues for external excitation light are the major obstacles for the wide application of photodynamic therapy (PDT). Nanocarriers provide an efficient way to deliver the photosensitizers. Compared with the upconversion nanoparticles and semiconductor quantum dots, the good biocompatibility, surface modification, and many other advantages of carbon quantum dots (CDs), besides the comparable fluorescent properties, make it easy to win out in the field of PDT. While the bioluminescence is generally in the visible regions, which is adjacent to or overlapped with the main absorption bands of present photosensitizers. Furthermore, the bioluminescence could served as a internal light to activate the photosensitizer and then the limitation of light penetration is of no concern. Therefore, in this project we propose to synthesize high luminescent CDs with folic acid (Fa) decorated in the surface (named Fa-N-Mg-CDs) by a Mg/N double doping strategy using suitable carbon source with Fa mixed, surface passivation agent containing nitrogen and magnesium salts through a hydrothermal method. The growth process and tunable photoluminescence mechanism of Fa-N-Mg-CDs will be illuminated. On this basis, the photosensitizer chlorin E6 (Ce6) and Renilla luciferase 8 (Rluc8) are immobilized on the surface of Fa-N-Mg-CDs through chemical coupling reactions to form a new bioluminescence triggered photosensitizer (called Rluc8-CDs-Ce6). The fluorescence resonance energy transfer between Rluc8, CDs and Ce6 will be studied. Meanwhile, the photodynamic fluorescence imaging and PDT effeciency will be explored. The bioluminescence triggered RLuc8-CDs-Ce6 is expected to be an ideal photosensitizer for PDT of tumors.

英文关键词： carbon quantum dots ;photodynamic therapy;bioluminescence;photosensitizer;tumor