Nitric Oxide, Singlet Oxygen, and Peroxynitrite Release from Anthraquinone Photodonor Liposomes with Colorimetric and...

Nitric oxide (NO) exhibits diverse therapeutic effects in biological systems. Recently, light-activated N-nitrosated NO donors with fluorescence and colorimetric responses have attracted considerable attention. Anthraquinones, known for their strong colorimetric and emissive properties as well as singlet oxygen (¹O₂) generation under light irradiation, remain largely unexplored as NO photodonors. Herein, we report the synthesis of an amphiphilic anthraquinone-based NO photodonor (Ant-NO) by incorporating an N-nitroso moiety. Upon light irradiation, Ant-NO efficiently releases NO, accompanied by distinct fluorescence and color changes. Embedding Ant-NO into the phospholipid DOPC yielded biocompatible, water-dispersible liposomal nanoassemblies (Ant-NO.Ves). The NO release behavior of Ant-NO and Ant-NO.Ves was investigated by time-dependent UV-vis absorption, fluorescence spectroscopy and the Griess assay. The photoinduced NO release rate constants were 0.15445 min^-1 (t_1/2 = 4.5 min) in acetonitrile and 0.36187 min^-1 (t_1/2 = 1.9 min) for the liposomal formulation. Notably, Ant-NO.Ves generated both NO and singlet oxygen upon light exposure. In vitro anticancer studies on HCT cells revealed significant light-induced cytotoxicity due to the synergistic production of NO and ¹O₂. Furthermore, Ant-NO.Ves enabled real-time fluorescent bioimaging in HCT cells, showing red emission during NO release and allowing visualization of intracellular NO dynamics.