A self-immolative near-infrared fluorescent probe for identification of cancer cells and facilitating its apoptosis

Abstract

Hydrogen sulfide (H₂S) plays a significant role in the onset and progression of cancer. It has led to increased interest in its potential as a diagnostic tool owing to its overexpression in cancer. However, research into the anti-cancer activity of H₂S, particularly its ability to promote apoptosis, is hindered by the lack of effective detection tools. To gain a comprehensive understanding of the targeted efficacy of H₂S in promoting cancer cell apoptosis, we designed and synthesized a self-immolative near-infrared fluorescent diagnostic probe, named YH-NO₂. The activation of this self-immolative reaction is dependent on the presence of nitroreductase (NTR) overexpressed in tumor cells. The design of YH-NO₂ involves releasing fluorophores through the activated self-immolative reaction for detection, while simultaneously releasing H₂S-loaded self-immolative spacers to promote cancer cell apoptosis. Consequently, YH-NO₂ achieves a seamless integration of recognizing and promoting cancer cell apoptosis through its self-immolative structure. This dual function allows YH-NO₂ to recognize NTR activity in cells under varying hypoxia levels and differentiate between normal cells and cancer cells using imaging technology. Notably, YH-NO₂ exhibits remarkable stability in cellular environments, providing controlled and selective H₂S release, thereby targeting the elimination of cancer cells through the promotion of apoptosis. Furthermore, in vivo experiments have demonstrated that YH-NO₂ can accurately identify tumor tissue and effectively reduce its size by utilizing its apoptosis-promoting properties. These findings not only provide further evidence for the anti-cancer activity of H₂S but also offer valuable tools for understanding the complex relationship between H₂S and cancer.

Keywords: Apoptosis; Cancer cells; Hydrogen sulfide; In vivo imaging; Self-immolative reaction.