Synergistic Luminescent Radicals and Precursors as Type-I Photosensitizers for Near-infrared Fluorescence-guided Tumor Therapy

Near-infrared (NIR) fluorescence-guided photodynamic therapy (PDT) shows great potential as a cancer treatment modality. However, its application in solid tumors is limited by the scarcity of NIR molecules and the oxygen dependence of conventional photosensitizers. Here, two novel radical nanoparticles (TTM-3PDMAC:HTTM-3PDMAC@NPs and TTM-PDMAC:HTTM-PDMAC@NPs) are developed as type-I photosensitizers by combining luminescent radicals and their precursors. The unique encapsulation of these nanoparticles effectively addresses the limitations of radicals being insoluble and non-fluorescent in water, thus preserving the NIR emission of the radicals. Notably, the superoxide radicals generated by these nanoparticles upon light irradiation have been demonstrated to originate from both the radicals and their precursors. In vivo experiments demonstrated that TTM-3PDMAC:HTTM-3PDMAC@NPs exhibit significant efficacy in treating hypoxic tumor with minimal side effects. Overall, this PDT strategy based on synergistic combination of luminescent radicals and precursors provides novel insights for achieving accurate and efficient PDT under NIR fluorescence guidance.