树枝状酞菁酶激活光动力分子信标的合成与抗肿瘤活性研究

项目名称： 树枝状酞菁酶激活光动力分子信标的合成与抗肿瘤活性研究

项目编号： No.21274021

项目类型： 面上项目

立项/批准年度： 2013

项目学科： 数理科学和化学

项目作者： 彭亦如

作者单位： 福建师范大学

项目金额： 82万元

中文摘要： 光敏剂的非特异性定位和激活是目前PDT面临的主要问题。为了提高光敏剂的肿瘤选择性，本课题合成系列具有靶向运输和靶分子特异性激活功能的树枝状酞菁酶激活光动力分子信标(PPMB)，用于诊断和治疗神经胶质瘤。PPMB由树枝状酞菁光敏剂，荧光猝灭剂和胶质瘤特异性连接体三部分耦联合成。胶质瘤过度表达酶为标靶分子，无标靶时，光敏剂荧光猝灭；有标靶时，标靶特异性识别和剪切连接体, 光敏剂产生荧光和单线态氧。研究"折叠"和"拉链"结构PPMB的合成方法，表征其结构、光物理性质和酶激活特异性和灵敏度。离体和动物模型实验研究PPMB对胶质瘤细胞的摄取规律，评价其治疗胶质瘤光动力活性。研究PPMB介导PDT诱导细胞凋亡的分子通道和PPMB－PDT诱导基质蛋白酶活性变化的高分辨时空成像，阐述PPMB介导的PDT治疗胶质瘤的分子机制。总结构效关系，为光敏剂新的靶向运输途径和特异性激活机制开发提供理论和实验依据。

中文关键词： 树枝状酞菁；光动力治疗；激活纳米光敏剂；分子成像；恶性肿瘤

英文摘要： Photodynamic therapy (PDT) is an emergying cancer treatment modality involving the combination of light，a photosensitizer and an oxygen. It offer unique control the photosensitizers（PS） 's action because the key cytotoxic agent, singlet oxygen is produced only in situ upon irradiation. However, PDT can't achieve a high level of selectivity because of the limited tumor localization of the exsiting PS, which in turn cause treatment-related toxicity to surrounding normal tissue as well as sunlight-induced skin toxicity. A new direction for PDT is to exert control of the PS' s ability to produce 1O2. This level control has potential to achieve ultimate PDT selectivity to cancer cell while leaving normal cells unharmed. Photodynamic molecular beacons is an extension of the well known molecular beacons (MB) that use the FRET principle for controlling fluorescence emission in response to target activation. By combining MB with PDT, we seek to enable cancer biomarker-controlled 1O2 production to achieve unprecedented PDT selectivity. In this proposal, we plane to synthesis and characterization a serials of novel dendrimer phthalocyanine based protease control activation photodynamic molecular beacons (PPMB), and demonstrated its utility for image and therapy of neuroglioma in vitro and in vivo. The PPMB comprises thr

英文关键词： dendrimer phthalocynine；photodynamic therapy；activation nanoactivation；molecular imaging；tumor