NIR-II Emissive Superoxide Radical Photogenerator for Photothermal/Photodynamic Therapy against Hypoxic Tumor

Due to the "Achilles' heels" of hypoxia, complicated location in solid tumor, small molecular photosensitizers with second near-infrared window (NIR-II) fluorescence, type-I photodynamic therapy (PDT), and photothermal therapy (PTT) have attracted great attention. However, these photosensitizers are still few but yet challenging. Herein, an "all in one" NIR-II acceptor-donor-acceptor fused-ring photosensitizer, Y6-Th, is presented for the in-depth diagnosis and efficient treatment of cancer. Benefiting from the strong intramolecular charge transfer, promoted highly efficient intersystem crossing, largely p-conjugated fused-ring structure, and reduced planarity, the fabricated nanoparticles (Y6-Th nanoparticles) can emit NIR-II fluorescence with the peak located at 1020 nm, exclusively generate O2 center dot- for type-I PDT, and display excellent PTT performance under an 808 nm laser stimulation. These characteristics make Y6-Th a distinguished NIR-wavelength-triggered phototheranostic agent, which can effectively therapy the hypoxic tumor using NIR-II-fluorescence-guided type-I PDT/PTT. This work provides a valuable guideline for fabricating high-performing NIR-II emissive superoxide radical photogenerators. An "all in one" acceptor-donor-acceptor fused-ring photosensitizer (Y6-Th) with both bright second near-infrared window (NIR-II) emission with high quantum yield (1.9%), exclusive O2 center dot--generating ability, and excellent photothermal therapy performance (photothermal conversion efficiency of 75.8%) is designed for type-I photothermal/photodynamic synergistic therapy against hypoxic tumor. This work provides a valuable guideline for developing high-performance NIR-II emissive superoxide radical phototheranostic agents. image