酞菁敏化Ru-arene配合物的PCT抗肿瘤研究

Photochemotherapy (PCT) that uses visible light for cancer therapy assistance, has become a hot topic in anticancer research for its low systemic toxicity and high selectivity. In this project, the strategies and methods of PCT study are fully used, and the chemical and biological properties of the center metal ions and ligands are comprehensively considered. Ru(II)-arene complexes containing photosensitized phthalocyanines (Pcs) are synthesized, in which the phthalocyanine derivatives are employed as bidentate ligands, and bioactive molecules such as NO, CO, CH3CN, pyridine derivative, cyanouracil, or econazole are employed as monodentate ligands. The obtained complexes are studied for their application in antitumor photochemotherapy. The structures, luminescence and the PCT antitumor activities of the Ru(II)-arene complexes and their structure-activity relationship are systematically investigated. Furthermore, the PCT mechanism of the complexes is thoroughly studied through the investigation of the production of singlet oxygen photosensitized by the Ru(II)-arene complexes, the binding of complex with DNA as well as the photorelease of the bioactive molecules induced by the light-induced ligand substitution reactions. The influence of the structure of the Ru(II)-arene complexes on their PCT mechanism will be further revealed, and the model of PCT mechanism of these complexes will be established. New thoughts and method will be explored for the design and application of PCT drugs, which will promote the development of PCT.

光化学疗法(PCT)是利用光照辅助癌症治疗的方法，因其系统毒性低、选择性高的优点，成为当前抗肿瘤研究的热点。本课题充分借鉴PCT研究的策略和方法，综合考虑中心金属离子和配体的化学、生物学性质，以酞菁衍生物作为光敏性双齿配体基团，以NO、CO、乙腈、吡啶衍生物、氰基尿嘧啶、益康唑等生物活性分子为单齿配体基团，合成新型光敏性Ru(II)-arene-Pc配合物，进行PCT抗肿瘤作用探讨。系统研究配合物分子结构、光谱学性质以及PCT抗肿瘤活性之间的构效关系。通过研究配合物光致产生单线态氧的量子产率，光致配体取代反应引发的配合物与DNA的结合，以及活性分子的释放作为额外活性组分的作用等三个方面，深入探讨其PCT作用机理，进一步揭示配合物分子结构对PCT作用机制的影响，建立作用机制模型。探索PCT抗肿瘤药物设计应用的新思路和方法，同时也将推动PCT抗肿瘤技术的发展。

光化学疗法(PCT)是利用光照辅助癌症治疗的方法，因其系统毒性低、选择性高的优点，成为当前抗肿瘤研究的热点。本课题选择具有良好抗肿瘤活性的芳基钌配合物和具有优良的光动力效应的卟啉、酞菁作为研究对象，进行PCT抗肿瘤作用探究。利用氨基硫脲衍生物、姜黄素衍生物等为配体，与芳基钌配位，合成了一系列新型结构的Ru(II)-arene配合物，并筛选出一批具有优良PCT肿瘤细胞抑制活性的配合物分子，并深入研究了它们的分子结构及其对肿瘤细胞的抑制活性之间的关系。利用卟啉衍生物Ce6负载于金纳米棒的二氧化硅涂层介孔中制备成纳米材料(AuNR@SiO2-NH2-Ce6)，表现出协同光热效应和单线态氧局部生成特性，对细菌的光灭活效果比单独的Ce6分子更强。AuNR@SiO2-NH2-Ce6可以固定在细胞膜上，并在细胞内部积聚。AuNR@SiO2-NH2独特的多孔结构使Ce6被封装在介孔中，并随后被光热效应释放和激活，使生成的单线态氧穿透细胞质膜或直接进入细菌细胞内部，从而克服了单线态氧寿命短的固有缺陷。AuNR@SiO2-NH2-Ce6不仅破坏了细菌细胞膜的完整性，而且在光照射下，促进了外部纳米材料在细菌中的细胞渗透和积累。此外，AuNR@SiO2-NH2-Ce6对哺乳动物细胞的细胞毒性和溶血活性可以忽略不计。因此，AuNR@SiO2-NH2-Ce6可能是极有前途的外用抗菌剂候选药物。