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 (¹O₂) 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 ¹O₂ 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 ¹O₂ 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.