Dual-activated fluorescent probe for the study of the mechanism of SO2 and NO in cisplatin resistance of nasopharyngeal carcinoma

Abstract

Cisplatin is widely used in the treatment of advanced nasopharyngeal carcinoma; however, its therapeutic application is often limited by a high incidence of drug resistance. Recent studies have demonstrated that nitric oxide (NO) and sulfur dioxide (SO₂), acting as gaseous signaling molecules, exhibit anti-cisplatin resistance properties in tumor cells. Nevertheless, developing appropriate chemical tools to investigate the mechanisms underlying NO and SO₂ mediated cisplatin resistance to cisplatin remains challenging. This study designed and synthesized a dual-responsive fluorescent probe to detect peroxynitrite (ONOO⁻) and SO₂, enabling them to be visualized within cells. Using this probe to detect and image ONOO⁻ and SO₂ in cisplatin-resistant cell lines revealed that NO and SO₂ combat cisplatin resistance by generating highly reactive ONOO⁻ and depleting intracellular glutathione. The IC₅₀ values of cisplatin-resistant cells treated with NO and SO₂ were significantly lower than those of the control group. These results indicate that HCy–ONOO⁻–SO₂ can serve as a powerful chemical tool for investigating the mechanisms of cisplatin resistance in nasopharyngeal carcinoma.