Engineering of cyanine-based nanoplatform with tunable response toward reactive species for ratiometric NIR-II fluorescent imaging in mice

High-quality second near-infrared (NIR-II) nanoprobes are of great significance for real-time bioimaging and medical diagnosis. Cyanine is an important class of fluorophores to construct activatable probes; however, there are still significant challenges hindering their biological applications, including weak fluorescence in aqueous solution, instability, and insufficient specificity. Herein, an integrated engineering strategy is conducted to develop the cyanine-based activatable NIR-II nanoplatforms with bright, stable emission and high specificity. Specifically, poly(styrene-co-maleic anhydride) (PSMA) is employed to encapsulate NIR-II fluorescent molecules (IR1048) to render the stable and bright NIR-II nanoparticles (PSMA@IR1048 NPs). By charge-modulated strategy, a series of cyanine-fluorophores are loaded on the surface of PSMA@IR1048 NPs and exhibit tunable response toward reactive species. Combing those two strategies, NIR-II ratiometric fluorescent nanoprobes (RNPs, including RNP1, RNP2, and RNP3) are constructed; among them, RNP2 displays hypochlorous acid (HClO) responsive performance and generates a higher NIR-II fluorescent ratio (FL2/FL1) signal. Such nanoprobe can reliably report the pathological HClO level in models of diabetic liver injury and lower limb ischemia–reperfusion (I/R) injury mice. Our study paves an engineering strategy to construct cyanine-based stable, bright, and specific NIR-II probes for bioimaging.