Xie Lina, Chen Zhuoli, Wang Tianying, Liang Jinzhe, Lie Qiaoshan, Jin Chengzhi, Zhang Xiting, Chen Yu, Chao Hui
MOE Key Laboratory of Bioinorganic and Synthetic Chemistry, State Key Laboratory of Anti-Infective Drug Discovery and Development, Guangdong Basic Research Center of Excellence for Functional Molecular Engineering, School of Chemistry, Sun Yat-Sen University Guangzhou 510006 P. R. China
Huangpu Hydrogen Innovation Center, Guangzhou Key Laboratory for Clean Energy and Materials, School of Chemistry and Chemical Engineering, Guangzhou University Guangzhou 510006 P. R. China
Chem Sci. 2025 Jul 10. doi: 10.1039/d5sc04006j.
The complexity of solid tumors in terms of light scattering, oxygen insufficiency, and redox imbalance complicates the strategic design of photoactivated therapy. In this work, an unprecedented photoactivated homolysis process of ferrocene is driven by the photochemistry of a conjugated cyclometalated iridium(iii) complex upon 970 nm three-photon excitation, exhibiting photo-uncaging, biocatalysis, and an ROS storm all in one moiety. Trapping assays, ultrafast spectroscopy, and DFT calculations reveal the release of Fe ions, the location of carbon-centered radicals, and the essential single electron transfer (SET) process for their generation. Such a photo-uncaging pattern harnesses peripheral substrates (O, HO and HO) for ROS generation. It continuously degrades the biomolecule homeostasis (GSH and NADH), inducing high immunogenic ferroptosis and necroptosis in hypoxic melanoma models for long-term photoimmunotherapy. The uncaging of the photostable ferrocene by transition metal photochemistry develops an elegant paradigm for multi-functional molecular photoactivated therapy.
实体瘤在光散射、氧气不足和氧化还原失衡方面的复杂性使光活化疗法的战略设计变得复杂。在这项工作中，在970 nm三光子激发下，共轭环金属化铱(iii)配合物的光化学驱动了前所未有的二茂铁光活化均裂过程，在一个部分中展现出光解笼、生物催化和ROS爆发。捕获实验、超快光谱和密度泛函理论计算揭示了铁离子的释放、碳中心自由基的位置以及它们产生所必需的单电子转移(SET)过程。这种光解笼模式利用外周底物(O、HO和HO)产生ROS。它持续破坏生物分子稳态(GSH和NADH)，在缺氧黑色素瘤模型中诱导高度免疫原性的铁死亡和坏死性凋亡，用于长期光免疫治疗。通过过渡金属光化学对光稳定二茂铁进行解笼，为多功能分子光活化疗法开发了一种优雅的范例。
