Construction of Type I Aggregation-Induced Emission Photosensitizers for Photodynamic Therapy via Photoinduced Electron Transfer Mechanism  

利用光诱导电子转移机制构筑Ⅰ型聚集诱导发光光敏剂用于光动力治疗

作　　者：Jia Hanyu Yu Yuewen Feng Guangxue Tang Ben Zhong 贾涵羽;俞岳文;冯光雪;唐本忠(华南理工大学材料科学与工程学院发光材料与器件国家重点实验室、广东省分子聚集发光重点实验室,广州510640;香港中文大学(深圳)理工学院、深圳分子聚集体科学与工程研究院,广东深圳518172)

机构地区：[1]Guangdong Provincial Key Laboratory of Luminescence from Molecular Aggregates,State Key Laboratory of Luminescent Materials and Devices,School of Materials Science and Engineering,South China University of Technology,Guangzhou 510640 [2]Shenzhen Institute of Aggregate Science and Technology,School of Science and Engineering,The Chinese University of Hong Kong,Shenzhen,Guangdong 518172

出　　处：《有机化学》2024年第8期2530-2537,共8页Chinese Journal of Organic Chemistry

基　　金：广州市应用基础研究计划项目(No.2024A04J2466);国家自然科学基金委青年科学基金(No.22205067);广东省分子聚集发光重点实验室(No.2023B1212060003)资助项目。

摘　　要：Photodynamic therapy(PDT)as a non-invasive anticancer modality has received increasing attention due to its advantages of noninvasiveness,high temporospatial selectivity,simple and controllable operation,etc.PDT mainly relies on the generation of toxic reactive oxygen species(ROS)by photosensitizers(PSs)under the light irradiation to cause cancer cell apoptosis and death.However,solid tumors usually exhibit an inherent hypoxic microenvironment,which greatly limits the PDT efficacy of these high oxygen-dependent conventional type II PSs.Therefore,it is of great importance to design and develop efficient type I PSs that are less oxygen-dependent for the treatment of hypoxic tumors.Herein,a new strategy for the preparation of efficient type I PSs by introducing the photoinduced electron transfer(PET)mechanism is reported.DR-NO_(2) is obtained by introducing 4-nitrobenzyl to(Z)-2-(5-(4-(diethylamino)-2-hydroxybenzylidene)-4-oxo-3-phenylthiazolidin-2-ylidene)malononitrile(DR-OH)with aggregation-induced emission(AIE)feature.The AIE feature ensures their high ROS generation efficiency in aggregate,and the PET process leads to fluorescence quenching of DR-NO_(2) to promote triplet state formation,which also promotes intramolecular charge separation and electron transfer that is conducive for type I ROS particularly superoxide radicals generation.In addition,DR-NO_(2) nanoparticles are prepared by nanoprecipitation to possess nanoscaled sizes,high cancer cell uptake,and excellent type I ROS generation ability,which results in an excellent performance in PDT ablation of MCF-7 cancer cells.This PET strategy for the development of type I PSs possesses great potential for PDT applications against hypoxic tumors.光动力治疗(PDT)作为一种非侵入性抗癌方式,凭借其低毒、高时空选择性及操作简捷可控等优势受到越来越多的关注.光动力治疗主要依靠光敏剂在特定激发波长光源照射下产生活性氧(ROS)以消融癌细胞.然而,乏氧是实体肿瘤的固有属性,而传统的II型光敏剂对氧气依赖度高,制约着PDT的治疗效果.因此,设计开发对氧气依赖度低的I型光敏剂用于抗肿瘤具有重要研究意义.报道了一种通过引入光诱导电子转移(PET)机制制备高效I型光敏剂的设计策略.通过在具有聚集诱导发光(AIE)活性的(Z)-2-(5-(4-(二乙氨基)-2-羟基亚苄基)-4-氧代-3-苯基噻唑烷-2-亚基)丙二腈(DR-OH)上引入4-硝基苄基,得到光敏剂DR-NO_(2),光激发后会发生PET过程,使得DR-NO_(2)的荧光得到一定程度的淬灭,促进三线态产生,同时还促进分子内电荷分离和更有效的分子内电子转移,进而促进其I型ROS尤其是超氧自由基的产生.此外,通过纳米工程制备得到DR-NO_(2)纳米粒子具有较小的纳米尺寸、优秀的肿瘤细胞摄取能力以及进一步增强的I型ROS产生能力,在光照下对MCF-7细胞展现出优秀的PDT杀伤能力.这种PET策略开发的I型ROS的光敏剂在抗乏氧肿瘤PDT应用中具有巨大潜力.

关 键 词：photodynamic therapy aggregation-induced emission photoinduced electron transfer type I photosensitizer hypoxic tumor microenvironment 

分 类 号：R73-36[医药卫生—肿瘤] TQ422[医药卫生—临床医学]