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 O2 ) 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.