College of Chemistry, State Key Laboratory of Photocatalysis on Energy and Environment, Fujian Provincial Key Laboratory of Cancer Metastasis Chemoprevention and Chemotherapy, Fuzhou University, Fuzhou, 350116, China.
Department of Pharmacy, The Affiliated First Hospital of Fujian Medical University, Fuzhou, 350001, China.
Eur J Med Chem. 2018 Jul 15;155:24-33. doi: 10.1016/j.ejmech.2018.05.039. Epub 2018 May 26.
A series of novel symmetric or unsymmetric silicon (IV) phthalocyanines axially substituted with cyclic Arg-Gly-Asp (cRGD) ligands through different ethylene glycol chains have been synthesized by a facile and mild "click" reaction. All the compounds show efficient photosensitizing activities in N,N-dimethylformamide, and are essentially non-aggregated in RPMI 1640 medium with 0.05% Cremophor EL. Owing to the presence of two cRGD ligands, the conjugate 6b exhibits highest selectivity toward αβ HT-29 cells in photocytotoxicities. It shows higher cellular uptake and ROS generation efficiency toward the αβ HT-29 cells compared with that of αβ MCF-7 cells. The competitive cellular uptake and subcellular localization indicate that 6b is internalized mainly through integrin-mediated endocytosis. In addition, the in vivo studies showed that 6b can mainly accumulate in tumor sites and show a significant PDT effect resulting in 75% tumor growth inhibition. The results indicate that 6b is a highly promising photosensitizer for targeted photodynamic therapy.
一系列新型的对称或非对称硅（IV）酞菁化合物通过不同的乙二醇链通过轴向取代环 Arg-Gly-Asp（cRGD）配体被合成，采用了一种简单温和的“点击”反应。所有化合物在 N,N-二甲基甲酰胺中均显示出高效的光致敏化活性，并且在 RPMI 1640 培养基中基本上没有聚集，其中含有 0.05%的 Cremophor EL。由于存在两个 cRGD 配体，缀合物 6b 在光细胞毒性方面对 αβ HT-29 细胞表现出最高的选择性。与 αβ MCF-7 细胞相比，它对 αβ HT-29 细胞具有更高的细胞摄取和 ROS 生成效率。竞争细胞摄取和亚细胞定位表明，6b 主要通过整联蛋白介导的内吞作用被内化。此外，体内研究表明，6b 主要可以在肿瘤部位积累，并表现出显著的 PDT 效应，导致 75%的肿瘤生长抑制。结果表明，6b 是一种很有前途的用于靶向光动力治疗的光敏剂。
