Development of a Near-Infrared Probe for Enhancing Cancer Therapy by Mitigating Pyroptosis-Induced Inflammation

Pyroptosis, a specialized cell death mechanism crucial in cancer therapy, is distinct from apoptosis and primary necrosis. It is linked to inflammation and reactive oxygen species, particularly peroxynitrite (ONOO^-), which is implicated in disease. Monitoring pyroptosis is challenging due to its connection with cellular polarity and the tumor environment. In this research, we developed a near-infrared probe, PBQI, which is highly sensitive and responsive to polarity and ONOO^- fluctuations. PBQI targets mitochondria and lipid droplets, enabling real-time tracking of pyroptosis-associated subcellular alterations. It was found to differentiate between normal and cancer cells during pyroptosis triggered by cisplatin and metformin. To mitigate pyroptosis-induced inflammation, disulfiram was used as an inhibitor, significantly alleviating excessive inflammation. This study highlights PBQI's utility in studying the interplay between polarity, ONOO^-, and pyroptosis, and contributes to the development of more targeted cancer therapies that optimize pyroptosis's antitumor benefits while minimizing inflammatory side effects.