NIR‐II Light Activated Photosensitizer with Aggregation‐Induced Emission for Precise and Efficient Two‐Photon Photodynamic Cancer Cell Ablation

Near infrared (NIR) light excitable photosensitizers are highly desirable for photodynamic therapy with deep penetration. Herein, a NIR-II light (1200 nm) activated photosensitizer TQ-BTPE is designed with aggregation-induced singlet oxygen (O-1(2)) generation for two-photon photodynamic cancer cell ablation. TQ-BTPE shows good two-photon absorption and bright aggregation-induced NIR-I emission upon NIR-II laser excitation. The O-1(2) produced by TQ-BTPE in an aqueous medium is much more efficient than that of commercial photosensitizer Ce6 under white light irradiation. Upon NIR-II excitation, the two-photon photosensitization of TQ-BTPE is sevenfold higher than that of Ce6. The TQ-BTPE molecules internalized by HeLa cells are mostly located in lysosomes as small aggregate dots with homogeneous distribution inside the cells, which favors efficient photodynamic cell ablation. The two-photon photosensitization of TQ-BTPE upon NIR-I and NIR-II excitation shows higher O-1(2) generation efficiency than under NIR-I excitation owing to the larger two-photon absorption cross section at 920 nm. However, NIR-II light exhibits better biological tissue penetration capability after passing through a fresh pork tissue, which facilitates stronger two-photon photosensitization and better cancer cell ablation performance. This work highlights the promise of NIR-II light excitable photosensitizers for deep-tissue photodynamic therapy.