新型可激活超分子光敏剂的设计制备与构效关系

项目名称： 新型可激活超分子光敏剂的设计制备与构效关系

项目编号： No.21473033

项目类型： 面上项目

立项/批准年度： 2015

项目学科： 分析化学

项目作者： 黄剑东

作者单位： 福州大学

项目金额： 83万元

中文摘要： 光动力治疗是一种新兴的肿瘤治疗手段，发展性能优异的光敏剂是提高其疗效的关键。基于层状复合金属氢氧化物（LDH）可作为药物纳米载体的特性，针对轴向取代硅酞菁易因分子内光诱导电子转移（PET）效应而失活的特点，本项目提出构建在体内循环中无光敏活性的硅酞菁/叶酸修饰锌铝LDH插层组装新型可激活超分子光敏剂。即通过分子内PET效应和主体层间的限域效应抑制硅酞菁的光敏活性；利用LDH的纳米EPR效应和叶酸受体介导作用实现硅酞菁的靶向运送；借助LDH在癌细胞中的生物降解以及所产生的Zn2+的PET阻断效应，激活硅酞菁的光敏活性。项目将设计合成一系列不同组成结构特征的硅酞菁及其LDH组装体，评价其光物理和光化学性质、靶向降解释放特性、Zn2+激活效率和光动力抗癌活性，进而揭示该新型靶向激活型超分子光敏剂的构效关系。该研究对发展高效抗癌光敏剂、认知超分子功能材料的物理化学本质具有重要的理论和实际意义。

中文关键词： 硅酞菁；层状复合金属氢氧化物；光敏剂；光动力治疗；超分子

英文摘要： Photodynamic therapy is a new modality for the treatment of tumors, and the improvement of its therapeutic effects is primarily depended on using of excellent photosensitizers. Owning to many merits of layered double hydroxides (LDHs) as a drug nanocarrier, meanwhile, with a view to utilize the fact that the photosensitizing activities of axial substituted silicon (IV) phthalocyanine derivatives (SiPcs) can be easily quenched by intramolecular photoinduced electron transfer (PET) effect, in this project, we will construct a novel activatable supermolecular photosensitizer by intercalation of SiPc into folate-modified Zn-Al LDH, that does not show photosensitizing properties in circulation system. In this supermolecular photosensitizer, the photosensitizing activities of SiPc will be deactivated by PET effect as well as LDH host confinement effect. The supermolecular photosensitizer should be specifically transported to tumor tissue as a result of enhanced permeability and retention (EPR) effect and mediation of folate receptor. Moreover, the LDH should be dissolved in cancer cells and release Zn2+ ion to inhibit PET effect, resulting in the restoration of photosensitizing properties of SiPc. Herein, a series of well-designed SiPcs and the responding supermolecular assemblies will be designed and prepared, and the photophysical and photochemical properties, targeting release effect, the binding efficiency between Zn2+ ion and SiPc, the efficiency of activation, and photodynamic activities will be studied to reveal the structure-activity relationships of this kind of targeted activatable supermolecular photosensitizers. This project shows a novel idea. It not only shows promising applications in development of novel photosensitizer, but also is favorable for cognizing the novel phenomenon of supermolecular photochemistry, which presents great academic values.

英文关键词： Silicon phthalocyanine;Layered double hydroxides(LDHs);Photosensitizer;Photodynamic therapy;Supermolecule