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.