ATP诱导组装激发型光敏剂的构筑及其荧光成像指导光动力治疗

光敏剂是光动力治疗的核心，对其研究与开发具有重要的意义。传统光敏剂存在水溶液聚集导致的荧光猝灭与单线态氧产生效率降低，及肿瘤组织特异性差问题。本项目以肿瘤组织及细胞内高浓度的ATP为研究对象，基于主客体作用诱导组装及AIE染料聚集荧光增强原理，合成出对ATP有特异性荧光增强识别且能产生单线态氧的两亲受体及其组装体，并用于细胞及肿瘤组织荧光成像与光动力治疗。以具有红外/近红外发光及产生单线态氧的四苯乙烯或三苯胺为染料母体，引入不同的阴离子识别位点及亲/疏水基团，得到系列ATP识别两亲受体；系统研究ATP诱导两亲受体组装行为、荧光及光照产生单线态氧能力的变化，及在复杂体系ATP诱导组装与识别的影响；并研究组装体在癌细胞及肿瘤组织荧光成像及光动力治疗效果；揭示受体结构、组装体形貌、荧光及单线态氧间的依赖关系；得到新型有应用前景肿瘤靶向光敏剂。

Photodynamic therapy (PDT) as a non-invasive therapeutic assay has been widely used in clinical cancer treatment. It relies on the cytotoxicity of reactive oxygen species (ROS) generated from photosensitizers (PSs) upon light irradiation to kill cancer cells. Traditional PSs show strong aggregation in aqueous solution, which result in a significantly aggregation-caused quenching (ACQ) effect and decreasing their fluorescence and singlet oxygen generation quantum yields. Recently, the aggregation-induced emission fluorogens provided a new avenue for the designation of powerful PSs for their high emissive and high singlet oxygen generation quantum yield in aggregation state. In addition, tumor microenvironment (TME)-triggered PSs, also termed as activatable photosensitizers (aPSs), have captured extensive attention due to their controllable response to the specific microenvironment, i.e., low intracellular pH value, specific enzymes, hypoxia, and high concentration of GSH. These PSs keep silent in the native form even under light irradiation. However, the fluorescence and ROS generation could be recovered in tumor. Regarding the high concentration ATP in living cells and tumor, in this project, we will research ATP activatable photosensitizers with aggregation-induced emission characteristics for imaging-guided photodynamic therapy. We will synthesis a series of amphiphilic AIE-based receptors for recognition of ATP with both fluorescence turn on response and singlet oxygen generation under light irritation. These receptors adopt soluble molecular or soft aggregation state in aqueous solution with weak emission and poor singlet oxygen generation. After binding with ATP, larger aggregations were formed with strong emission and singlet oxygen generation ability. The binding mechanism will investigated. In addition, the AIE-based receptors will be used for cells and tumor imaging and photodynamic therapy.