Mitochondria-targeted NO donor enables synergistic NO and photodynamic therapies for effective inhibition of cancer cell proliferation and migration

Previously reported light-controlled nitric oxide donors are usually activated by blue or green light. The insufficient ability of short wavelength light to penetrate tissues and its potential phototoxicity to living organisms greatly restricted in vivo applications. This study presents the development of a novel mitochondria-targeted nitric oxide donor, R–NO, capable of controlled nitric oxide and photosensitizer release under white light irradiation in mitochondria. R–NO is capable of generating nitric oxide and R–NH, a novel photosensitizer that can produce O2•- upon irradiation with a single light source. In addition, the highly toxic ONOO− can be produced by the rapid reaction of nitric oxide and O2•-. Harnessing the synergistic effects of PDT, nitric oxide therapy and highly toxic ONOO−, the proliferation and migration of cancer cells can be significantly inhibited upon light irradiation with R–NO. Futhermore, our MTT experiments demonstrated that simultaneous producing of O2•- and nitric oxide in the same region is crucial for efficient cancer cell inhibition. These interesting findings underscore the enhanced synergistic effect achieved by combining PDT and NO therapy in a single molecule for cancer cell treatment.