Mitochondrion‐Anchored Photosensitizer with Near Infrared‐I Aggregation‐Induced Emission for Near Infrared‐II Two‐Photon Photodynamic Therapy
Zhenyan He, Yuting Gao, Huimin Zhang, Ying Xue, Fanling Meng, Liang Luo
Abstract
Abstract Two‐photon photodynamic therapy (2P‐PDT) that employs photosensitizers (PSs) with 2P absorption is particularly intriguing in cancer treatment, in that 2P excitation enables precise spatial localization and deep tissue penetration. Here, a donor‐ π ‐acceptor PS (named TPBPy) with near infrared (NIR) aggregation‐induced emission (AIE) is designed and synthesized for imaging‐guided 2P‐PDT. The maximal photoluminescence (PL) peak of TPBPy is as high as 720 nm when it is encapsulated in liposomes. Upon 2P irradiation by a laser in NIR‐II window ( λ = 1000 nm), TPBPy exhibits strong NIR‐I PL in a multicellular tumor spheroids (MCTSs) model, showing an imaging depth of 210 µm that is significantly higher than upon one‐photon irradiation. Moreover, TPBPy localizes specifically on mitochondrion, an important organelle in cell oxidative metabolism and apoptosis. When exposed to the NIR‐II irradiation, TPBPy can efficiently generate singlet oxygen ( 1 O 2 ) and trigger cell death. The efficacy of TPBPy‐mediated 2P‐PDT has also been validated using 4T1 tumor mouse model, the growth of which is significantly suppressed upon NIR‐II laser irradiation. TPBPy herein serves as an excellent candidate to suppress deep tumor tissues through NIR‐II 2P‐PDT, and also renders a new paradigm to construct mitochondrion‐anchored AIE luminogens for future cancer theranostic applications.