Real-time NIR-II fluorescence imaging-guided precision thrombolysis with a molecularly planarized phototheranostic agent

利用分子平面化光疗诊断剂进行实时近红外二区荧光成像引导的精准溶栓治疗

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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.

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