Photoactivated Lysosomal Escape of a Monofunctional PtII Complex Pt‐BDPA for Nucleus Access. Issue 36 (28th July 2019)

• Record Type: Journal Article
• Authors: Xue, Xuling; Qian, Chenggen; Fang, Hongbao; Liu, Hong‐Ke; Yuan, Hao; Guo, Zijian; Bai, Yang; He, Weijiang
• Is Part Of: Angewandte Chemie international edition. Volume 58:Issue 36(2019)
• Page Start: 12661
• Page End: 12666
• Publication Date: 2019-07-28
• Subjects: fluorescence imaging -- lysosomal escape -- photosensitizers -- platinum drugs -- Tumor; Chemistry -- Periodicals; 540
• DOI: 10.1002/anie.201906203
• Languages: English
• ISSNs: 1433-7851

Abstract

Abstract: A photosensitizing monofunctional Pt complex, Pt‐BDPA, was prepared with a BODIPY chromophore. Apart from its DNA binding ability, this complex displays emission at ca. 578 nm and a singlet oxygen quantum yield of 0.133. Confocal imaging revealed that this complex was sequestered in lysosomes via endocytosis in the dark, preventing its access to the nucleus. Profiting from its photoinduced ROS generation ability, this complex undergoes lysosomal escape to access the nucleus upon photoirradiation. The photoinduced ROS still cause a drop in intracellular GSH, favoring the stability of Pt‐BDPA and contributing to its nuclear DNA accessibility. This complex displayed distinct cytotoxicity to all tested tumor cell lines upon photoirradiation, and the IC50 values were ca. 3–6 μm, which are distinctly lower than those found with only dark incubation (IC50 >50 μm ). These results are consistent with photoactivated lysosomal escape of this photosensitizing Pt complex to access the nucleus. Abstract : The lysosome sequestration of photosensitizing Pt‐BDPA results in its lack of access to the nucleus and poor cytotoxicity. Short‐time photoirradiation causes the complex to undergo lysosomal escape to access the nucleus, distinctly promoting antitumor cytotoxicity.