An Efficient Heat and Peroxynitrite Generating Nanoplatform for Multimodal Imaging-guided Precision Tumor Phototherapy

Near-infrared II (NIR-II) fluorescent nanoparticles (NPs) based on aggregation-induced emission (AIE) have attracted significant attention due to their multimodal imaging capabilities as well as the combined photothermal and photodynamic therapeutic effects in cancer therapy. Reported herein is the rational designed AIE molecule (BPT), via incorporating phenothiazine units with strong electron-donating and reactive oxygen species (ROS) generation capabilities into the classical AIE scaffold tetraphenylethylene, further coupled with a strong electron-acceptor named benzo[1,2-c:4,5-c']bis[1,2,5]thiadiazole. The BPT NPs exhibited maximum NIR-II fluorescence emission at 1083 nm, a fluorescence quantum yield of 1.53%, photothermal conversion efficiency of 63%, and photoacoustic imaging capabilities, alongside considerable type I ROS generation ability. Additionally, when a kind of nitric oxide (NO) donor named O₂-(2,4-dinitrophenyl) 1-[(4-ethoxycarbonyl) piperazin-1-yl]diazen-1-ium-1,2-diolate (JSK) was incorporated, the corresponding JSK-BPT NPs could generate O₂⁻, NO, and peroxynitrite to induce phototoxicity. By applying it to the 4T1 breast tumor model, JSK-BPT NPs achieved high-quality multimodal imaging of the vasculature and tumor regions in mice. Under the multimodal imaging guidance, the 4T1 tumor could be ablated completely after a single dose of JSK-BPT NPs and under the irradiation of an 808 nm laser.