An hypochlorous acid-responsive NIR-IIb nanosensor for In Vivo monitoring of inflammatory bowel disease progression

Accurate assessment of inflammatory bowel disease (IBD) severity is crucial for optimizing treatment decisions and improving prognosis. However, conventional assessment methods are time-consuming and primarily detect anatomical changes at moderate or late stages, limiting timely intervention. Here, we report an HClO‑responsive NIR‑IIb ratiometric nanosensor (CSSS@PMH‑mPEG2000) that combines down‑conversion core-shell nanoparticles with strong NIR‑IIb emission under 808/980 nm excitation and an HClO‑responsive IR780MA dye. By means of dye sensitizing mechanism, the sensor enables dynamic ratiometric quantification of HClO and supports real-time assessment of IBD progression and severity. Comprehensive in vitro and in vivo studies validate CSSS@PMH‑mPEG2000 as a highly sensitive and reliable platform for real-time, quantitative HClO monitoring of IBD in a mouse model. Moreover, ratiometric NIR‑IIb fluorescence imaging effectively captures changes in disease severity, highlighting its potential for assessing treatment efficacy. Together, these findings underscore the translational value of CSSS@PMH‑mPEG2000 for advancing IBD diagnosis and management, while also demonstrating its broader applicability to in situ HClO detection across a range of inflammatory diseases. STATEMENT OF SIGNIFICANCE: Accurate IBD severity assessment is vital for optimizing treatment and prognosis, but conventional methods are time‑consuming and detect mainly mid‑to‑late anatomical changes, delaying intervention. We present an HClO‑responsive NIR‑IIb ratiometric nanosensor (CSSS@PMH‑mPEG2000) combining down‑conversion core-shell nanoparticles with an HClO‑responsive IR780MA dye. Using dye sensitizing mechanism, it enables dynamic ratiometric HClO quantification and real‑time evaluation of IBD progression and severity. In vitro and in vivo studies in a mouse IBD model demonstrate high sensitivity and reliability for real‑time, quantitative HClO monitoring. Ratiometric NIR‑IIb imaging captures disease‑severity changes and supports treatment‑efficacy assessment, underscoring the platform's translational value for IBD management and broader in situ HClO detection in inflammatory diseases.