NIR-II light-activated two-photon squaric acid dye with Type I photodynamics for antitumor therapy

Photodynamic therapy (PDT) for hypoxic tumors has attracted wide attention owing to its noninvasiveness, easy maneuverability, and instantaneity. However, hypoxia in tumors and penetration depth of conventional ultraviolet light has greatly weakened its performance. To solve these problems, under NIR-II light irradiation, squaric acid nanoparticles (SQ NPs) with superior reactive oxygen, especially, hydroxyl radicals (•OH) production performance were first utilized for hypoxic tumor therapy. SQ NPs with intense light capture capability, intense NIR emission, and excellent photobleaching resistance show continuous •OH generation capabilities under NIR-II laser excitation. Through the superior PDT performance, the growth of hypoxic tumors was effectively inhibited, and the survival rate of mice was improved. This work highlights the application of NIR-II photoexcitation in deep tissue type I photodynamic therapy of hypoxic tumors, which will facilitate the development of hypoxic tumor PDT in deep depth.