Exceptional Near-Infrared II Organic Small Molecule Nanoagent for Photoacoustic/Photothermal Imaging-Guided Highly Efficient Therapy in Cancer

Near-infrared II (NIR-II) photoacoustic (PA)/photothermal imaging-guided tumor therapy holds great promise in precision medicine for cancer treatment. This work reports on the synthesis and application of an organic small molecule nanoagent that has exceptional PA and photothermal properties in the near-infrared region. BCy-TPE was constructed by linking an NIR-II absorbing cyanine dye BCy-Cl with a twisted tetraphenylethene unit. The synthesized BCy-TPE exhibited an intense absorption peak at 1032 nm. After encapsulation into water-dispersible nanoparticles (NPs), BCy-TPE NPs exhibited two absorption peaks at 880 and 1046 nm. Notably, under 1064 nm laser excitation, BCy-TPE NPs deliver a remarkable photothermal conversion efficiency of 92%, together with superior biocompatibility, photostability, and PA/photothermal imaging capability. Moreover, after intravenous administration of BCy-TPE NPs into 4T1 tumor-bearing mice and treatment with safe-intensity (1.0 W cm-2 and 1064 nm) laser irradiation, tumor temperature increased rapidly to 52 °C within 1 min and tumors are completely ablated after a single photothermal therapy treatment. Overall, this work offers a novel strategy to develop superb NIR-II photothermal agents for PA/photothermal imaging-guided highly efficient therapy in cancer.