Cuproptosis accompanied by obvious •OH generation revealed with an ultrasensitive NIR fluorescence probe

Cuproptosis is a recently discovered copper-dependent pathway of regulated cell death, and may play a role in a number of physiological and pathological processes; however, the variation of reactive oxygen species such as center dot OH level is unclear during cuproptosis. Herein, we have developed an ultrasensitive near-infrared (NIR) fluorescence probe CDHQ for characterizing cuproptosis, which reveals an obvious hydroxyl radical (center dot OH) generation during cuproptosis. The specific hydrogen abstraction of center dot OH causes a large pi-conjugation extension and spectral shift of CDHQ, accompanied by a high-contrast fluorescence off-on response. CDHQ can detect trace center dot OH that is undetectable by other methods such as electron spin resonance during autoxidation of low-valent metals (Fe2+, Ti3+, V3+ and especially Cu+) in the absence of H2O2. Using CDHQ, we have found that center dot OH is significantly generated in the copper-overloaded cells of cuproptosis, even before cell death. Moreover, CDHQ is capable of monitoring the generation of center dot OH in living mice, and thus may be expected to be useful for studying the in vivo change of center dot OH in more biosystems.

Automated summary

The researchers have developed a near-infrared fluorescence probe CDHQ for studying cell death, which reveals the generation of hydroxyl radicals during this process. This probe can detect trace levels of hydroxyl radicals that cannot be detected by other methods.