A dual-positive charges strategy for sensitive and quantitative detection of mitochondrial SO2 in cancer cells and tumor tissue

Mitochondrial sulfur dioxide (SO2) correlates with various activities of the development and progression of cancer. However, the specific biological function of mitochondrial SO2 in cancerous cells remains amphibolous. Therefore, it is of great significance and urgency to develop a rapid and accurate method to monitor the dynamic fluctuations of mitochondrial SO2 in cancer cells and tumor tissue. Herein, in this work, we introduce a dualpositive charges strategy for simultaneously enhancing the sensitivity and mitochondrial targeting ability of SO2 detection in cancer cells for the first time. For proof of concept, the dual positive charged probe DCP was rationally designed and synthesized based on chromenoquinoline fluorophore. Correspondingly, we also synthesized single positive charged SO2 probe MCP as controls. As expected, the detection limit of dual positive charged DCP for SO2 detection was 0.06 mu M, which was 7-fold lower than that of the single positive charged probe MCP. Besides, DCP showed a higher mitochondrial co-localization coefficient in cancer cells and it could distinguish cancer cells (HeLa) and normal cells (L929) in co-incubated system. In a word, the evidence suggested that the implementation of dual-positive charges strategy greatly improved the sensitivity to SO2 response and the specificity of mitochondrial targeting in cancer cells. Finally, DCP was successfully applied to monitor SO2 fluctuation in cancer cells, tumor tissue and living zebrafish. Thus, this work provides a powerful tool to investigate the role of mitochondrial SO2 in cancer and other related diseases.

Automated summary

This study introduces a dual-positive charges strategy to enhance the sensitivity and mitochondrial targeting ability of sulfur dioxide (SO2) detection in cancer cells. The results demonstrate that the implementation of this strategy greatly improves the sensitivity to SO2 response and the specificity of mitochondrial targeting in cancer cells.