Hydrogen selenide in biological systems: from synthetic donors to fluorescent probes

Analogous to hydrogen sulfide (H₂S), the more strongly reductive hydrogen selenide (H₂Se) functions as a key endogenous mediator, exerting significant influence on signal transduction, redox regulation, and cytoprotection. However, the in vivo generation of H₂Se via molecular donors and the real-time monitoring of its fluctuations remain challenging due to inherent instability. To tackle these challenges, several H₂Se donors, including organic small molecule, inorganic salt, and composite nanoparticles, have been developed to ensure controlled H₂Se delivery. Meanwhile, various kinds of fluorescent probes have been developed as powerful tools for the real-time visualization of H₂Se at both cellular and organismal levels. This review will summarize the development of H₂Se donors and fluorescent probes and emphasize the underlying obstacles that still exist in this field, with the aim of providing a deeper understanding of the biological functions of endogenous H₂Se and facilitate its exploration across interdisciplinary fields.