Construction of an activatable ratiometric fluorescent nanoprobe for HClO detection and imaging in acute kidney injury models.

Acute kidney injury (AKI) is a prevalent and life-threatening clinical condition associated with substantial morbidity and mortality. Early diagnosis and prompt therapeutic intervention are therefore critical to improving patient prognosis. A hallmark pathophysiological feature of AKI-regardless of etiology, including ischemia/reperfusion injury, nephrotoxic drug exposure, or sepsis-is the burst-like overproduction of hypochlorous acid (HClO). Consequently, dynamic and quantitative monitoring of renal HClO levels not only advances our mechanistic understanding of AKI progression but also holds significant promise for early disease warning and real-time assessment of therapeutic efficacy. Herein, we developed an HClO-activatable ratiometric nanofluoroprobe, designated CHI-CBO, by covalently conjugating a small-molecule HClO-responsive fluorophore to glycol chitosan-a biocompatible and biodegradable natural polysaccharide. CHI-CBO exhibits a robust ratiometric fluorescence response to HClO and demonstrates prolonged renal retention, enabling sustained and high-fidelity imaging. Notably, CHI-CBO achieved high-performance dynamic ratiometric fluorescence imaging of endogenous HClO in living RAW264.7 macrophages and zebrafish embryos. Moreover, using CHI-CBO as an imaging agent, we successfully performed real-time, noninvasive ratiometric fluorescence imaging of HClO accumulation in the kidneys of a murine AKI model-thereby underscoring its translational potential for early AKI detection and monitoring.