Mitochondrial SO2-Activated NIR Photodiagnostic Agent Harnessing Hydroxyl Radicals for Efficient Inflammation Eradication and Tumor Suppression

At present, some progress has been made in developing NIR light-responsive free radical generators. However, the efficacy of theranostics continues to be hindered by tumor-associated inflammatory reactions. Hence, fulfilling the in situ release of free radicals upon NIR light excitation specifically activated by the inflammation microenvironment would be an ideal strategy for efficient inflammation eradication and tumor suppression but remains a challenge. Herein, a SO₂ (overexpressed reactive sulfur species in inflamed site)-stimulated phototheranostic agent (CVS) is successfully developed. Through a specific response to both endogenous and exogenous SO₂ with a low LOD (31.7 nM), CVS demonstrates the "switch on" two-photon activity as well as efficient OH· generation. Remarkably, in CVS-treated H22-tumor-bearing mice, the NIR light-activated accurate inflammation eradication and tumor suppression are accomplished. This reactive phototheranostic platform not only facilitates the quantification of SO₂ during inflammation but also renders it a potent NIR antihypoxic tumor agent.