Tumor Microenvironment-Activatable Phototheranostic: Leveraging Nitric Oxide and Weak Acidity as Dual Biomarkers for Ratiometric Fluorescence, Photoacoustic Imaging, and Photothermal Therapy.

Tumor microenvironment-responsive phototheranostic agents are highly sought after for their ability to improve diagnostic accuracy and treatment specificity. Here, we introduce a novel single-molecule probe, , which is activated by nitric oxide (NO) and weak acidity, enabling dual-mode imaging and photothermal therapy (PTT) of tumors. In acidic environments with elevated NO levels, exhibits a distinctive ratiometric fluorescence signal shift from the red to near-infrared, accompanied by a 700 nm photoacoustic signal. Additionally, demonstrated potent photothermal effects upon NO and acidity activation, achieving an impressive conversion efficiency of 74.3% under 735 nm laser irradiation. In vivo studies confirm 's ability to accurately image tumors through ratiometric fluorescence and photoacoustic modes while selectively treating tumors with PTT.