Real-time NIR-II Fluorescence Imaging-Guided Precision Thrombolysis with a Molecularly Planarized Phototheranostic Agent

Abstract

The precise diagnosis and treatment of intravascular thrombosis pose a major clinical challenge, as existing technologies struggle to simultaneously achieve high-resolution imaging and highly efficient yet safe therapy. To address this, we propose a molecular planarization engineering strategy. Based on the benzo[cd]indol-2(1H)-one scaffold, phenyl/biphenyl groups were introduced at the 6-position to construct a D-A-D type squaraine dye, SQ-BiPh. This strategy significantly extends the π-conjugation system and enhances molecular rigidity. Notably, the molecule forms a well-defined J-aggregate structure after nanoencapsulation, which substantially red-shifts the absorption peak to 1087 nm, extends the emission wavelength beyond 1130 nm, and simultaneously endows the material with excellent photothermal conversion performance.The corresponding nanoparticles (SQ-BiPh NPs) enable simultaneous high-contrast NIR-II fluorescence imaging and precise 1064 nm laser-triggered photothermal thrombolysis in a mouse model of lower-extremity venous thrombosis, allowing real-time monitoring of thrombus dissolution and vascular recanalization. This work not only establishes a new, generalizable molecular design paradigm for developing high-performance NIR-II phototheranostic agents but also successfully constructs an efficient, safe, and integrated platform for precise thrombus theranostics.