An AIE cyanine photosensitizer achieving hypoxic tumor ablation through synergistic treatment of type i photodynamic and photothermal therapy

In recent years, most photosensitizers suffer from poor photothermal conversion efficiency (PCE), vulnerability to aggregated-caused quenching under physiological conditions, and are highly dependent on oxygen, which seriously limit their application in cancer therapy. In this study, DTIR780 was an aggregation induced emission (AIE) photosensitizer, which was synthesized through the originality of molecular engineering. Because DTIR780 had a special organelle targeting lysosomes and mitochondria, it had excellent PCE (PCE = 28.9 %), and could simultaneously generate Type I reactive oxygen species (ROS): O 2 ·- and ·OH and Type II ROS: 1 O 2 , showing significantly enhanced tumor phototoxicity in both normoxia and hypoxic tumor microenvironments. In vivo testing demonstrated that DTIR780 NPs was efficiently accumulated at the tumor site while significantly inhibiting tumor growth in a subcutaneous H22 tumor mouse model. In summary, this lysosome and mitochondria targeted DTIR780 NPs has great potential in clinically image-guided type I photodynamic therapy (PDT) and photothermal therapy (PTT), offering a novel avenue for developing high-performance type I PDT/PTT photosensitizers for the efficient treatment of hypoxia tumors.