H 2 S-Activated Type-I Photochemical Probe: Fluorescent Self-Reporting for Real-Time Monitoring of Tumor Ablation

The fluorescent self-reporting probe-mediated photodynamic therapy (PDT) is an effective approach for tumor ablation. For tumor-specific targeting, there is a pressing need to develop a photochemical probe (PC-P) that selectively recognizes tumor-associated stimuli and simultaneously activates fluorescence self-reporting signals and phototoxicity. Herein, we developed NH₂-TPA-N, a H₂S-specific activatable PC-P that integrates self-reporting and phototoxic functionalities. NH₂-TPA-N exhibits a maximum absorption at 375 nm (ε = 4.12 × 10⁴ M^-1 cm^-1) but displays minimal fluorescence (λ_em = 445 nm, Φ = 1.38%) due to efficient nonradiative decay from the singlet excited state. Upon exposure to H₂S, NH₂-TPA-N undergoes a complete transformation into NH₂-TPA, with a reaction rate of 5.5-11.4 nM·S^-1 over 60 min and 16.6-30.7 nM·S^-1 over 30 min, respectively. This conversion triggered a significant fluorescence-on response: the fluorescence signal at 433 nm is significantly enhanced, increasing in intensity by 62-times (Φ: from 1.38 to 85.4%), thereby achieving a clear "OFF-ON" fluorescent self-reporting. Additionally, the electron transfer capability of activated NH₂-TPA in the singlet excited state is enhanced, as demonstrated by an 11.6-fold increase in the quenching constant with TCNQ. Consequently, type-I phototoxicity was effectively activated in 4T1 cells, resulting in substantial tumor growth inhibition in vivo (V_experimental/V_control = 0.12). Thus, NH₂-TPA-N not only serves as an efficient H₂S-activating PC-P but also enables real-time monitoring of tumor ablation through robust fluorescent self-reporting. It provides a valuable platform for precise tumors treatment with real-time spectral feedback and offers a rational strategy for the design of activatable PC-P.