Harnessing donor cyclization strategy: Converting type II to type I photosensitizers and enhancing AIE performance for NIR-II FL/MR imaging-guided photodynamic therapy under hypoxia condition

•Donor cyclization strategy to convert Type II into Type I photosensitizers.•NIR-II emitting AIE photosensitizers for FL/MR imaging guided PDT under hypoxic. Although type I photodynamic therapy (PDT) holds significant advantages in treating hypoxic tumors, limited design strategies for type I photosensitizers, as well as aggregation-caused quenching (ACQ), still hinder its broad application. Herein, a simple donor cyclization strategy is proposed to convert a type II photosensitizer YD-1 into type I photosensitizer YD-2, thereby shifting the predominant ROS production from singlet oxygen (1O2) to superoxide anion (O2•−). Compared to YD-1, YD-2 demonstrates superior aggregation-induced emission (AIE) performance. Furthermore, by incorporating a magnetic resonance (MR) imaging unit (Gd3+-chelated DOTA) onto the surface of DSPE-mPEG2000-NH2-encapsulated YD-2 to construct YD-2-Gd nanoparticles (NPs), which offers much better over single fluorescence (FL) imaging modality. In vivo, studies have demonstrated that YD-2-Gd NPs successfully achieved precise and effective PDT for tumors under the guidance of near-infrared-II (NIR-II) FL/MR dual-modal imaging, with no apparent toxic side effects. This work offers a straightforward and effective strategy for improving the precise and efficient treatment of hypoxic solid tumors, providing valuable guidance for designing type I photosensitizers with AIE activity.