基于pH响应解聚激活的抗肿瘤纳米光敏剂研究

项目名称： 基于pH响应解聚激活的抗肿瘤纳米光敏剂研究

项目编号： No.21301031

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： 柯美荣

作者单位： 福州大学

项目金额： 24万元

中文摘要： 光动力治疗是一种新兴的肿瘤治疗手段，光敏剂是决定其疗效的关键因素，如何进一步提高光敏剂的靶向性、避免对正常组织的损伤是当前该领域亟待解决的重要问题。基于锌酞菁光敏分子具有易聚集而自淬灭光敏活性的特性，并考虑到介孔二氧化硅纳米粒子生物相容性高且因EPR效应具有肿瘤组织选择性，本项目拟利用对细胞内pH敏感的连接基团，将锌酞菁负载到介孔二氧化硅纳米粒子上，并通过调整负载量，使其以无活性的聚集态存在，构建一种在体内循环过程中暂时无光敏化活性、但能够有效地在肿瘤细胞内通过pH响应解聚激活的纳米光敏剂。通过对不同组成结构特征的纳米光敏剂的制备、表征、光物理光化学性质、pH的响应情况、离体及活体生物活性的研究，揭示其构效关系，阐明具有肿瘤靶向性释药的纳米光敏剂应具备的结构特征。本项目的研究思路和研究内容新颖，其结果将为靶向抗癌光敏剂的设计提供新策略，具有重要的应用前景，并对促进学科交叉发展具有学术价值。

中文关键词： 酞菁；纳米光敏剂；光动力疗法；介孔二氧化硅纳米粒子；pH-响应

英文摘要： Photodynamic therapy (PDT) is a promising modality for the treatment of a variety of premalignant and malignant tumor, and the therapeutic effects are majorly depended on photosensitizers. To improve the tumor-targeting property of photosensitizers and avoid damage to normal tissue are some urgent issues to solve for PDT. Considering the intrinsic aggregation tendency of zinc (II) phthalocyanine molecules to result in self-quenching, and the high biocompatibility and enhanced permeability and retention (EPR) effect of mesoporous silica nanoparticles (MSN), which will enhance the tumor selectivity, in this project, we will conjugate zinc (II) phthalocyanines with MSN through an endo-/lysosomal pH-responsive linker to form inactive photosensitizers as a result of aggregation through regulating the loading of photosensitizers, and construct a nanoparticle-based photosensitizer activated by pH-responsive disaggregation, which does not show photosensitizing properties during circulation in the body and can release the photosensitizers into tumor cells efficiently. A series of different nanoparticle-based photosensitizers will be prepared and characterized, and their photophysical and photochemical properties, pH-response, in vitro and in vivo activities are also going to be investigated to demonstrate the structure-a

英文关键词： phthalocyanine；nano-photosensitizer；photodynamic therapy；Mesoporous silica nanoparticle；pH-responsive