Effective One‐for‐All Phototheranostic Agent for Hypoxia‐Tolerant NIR‐II Fluorescent/PA Image‐Guided Phototherapy

Near-infrared (NIR)-triggered type-I photosensitizers are crucial to address the constraints of hypoxic tumor microenvironments in phototherapy; however, significant challenges remain. By selecting an electron-deficient unit, a matched energy gap in the upper-level state is instrumental in boosting the efficiency of intersystem crossing for the type-I electron transfer process. 2-Cyanothiazole, an electron acceptor, is covalently linked with N, N-diphenyl-4-(thiophen-2-yl)aniline to yield a multifunctional photosensitizer (TTNH) that exhibits intrinsic NIR absorbance and compatible T2 energy levels, facilitating both radiative and nonradiative transitions. The prepared nanoparticles (TTNH NPs) assembled from TTNH are activated by an 808 nm laser and generated the O2•- for hypoxia-tolerant type-I photodynamic therapy under both normoxia and hypoxic conditions. TTNH NPs emitted NIR-II fluorescence with an impressive NIR-II fluorescence quantum yield of 2.08%. With a high photothermal conversion efficiency of 51.8% under 808 nm laser stimulation, TTNH NPs exhibit photothermal therapy performance, accompanied by enhanced photoacoustic imaging capability owing to their strong NIR absorption. These characteristics make TTNH an effective NIR-wavelength-triggered phototheranostic agent that outperforms NIR-II fluorescence/photoacoustic dual-model imaging-guided type-I photodynamic therapy/photothermal therapy against hypoxic tumors. This results provide valuable insight for developing high-performance NIR-II-emissive superoxide radical phototheranostic agents.