Ratiometric Nanoprobes With Emission Beyond 1600 nm for In Vivo Inflammation Detection

Abstract Near‐infrared ratiometric imaging holds significant promise for real‐time in vivo detection and spatial mapping of inflammation across physiological and pathological contexts. However, conventional nanoprobes are constrained by emission wavelengths below 1600 nm, limiting tissue penetration from scattering and absorption of endogenous chromophores. To address this, a ratiometric nanoprobe based on Tm 3+ ‐doped nanoparticle is engineered with emission at 1811 nm, to leverage deep‐tissue penetration and enhance signal‐to‐noise ratio under dual‐wavelength excitation, 808 nm and 980 nm. Conjugation with IR‐806, which is responsive to selective recognition of hypochlorite (ClO − ), enables the nanoprobe to give out analyte‐dependent emission under 808 nm excitation, while a stable, analyte‐independent reference signal under 980 nm irradiation. These two‐excitation‐mode and responsive emission benefit self‐calibration to mitigate non‐specific interferences. A detection limit of 300 nM is achieved for inflammatory marker, ClO − , surpassing the sensitivity required for inflammatory diagnosis. Benefiting from the dual long‐wavelength excitation and emission modalities, precise dynamic ratiometric imaging of ClO − is achieved in deep tissues. The nanoprobe successfully maps the inflammation sites and monitors ClO − fluctuations in arthritis and intestinal inflammation. These findings advance the design of second near‐infrared (NIR‐II) ratiometric nanoprobes and hold promise for in vivo diagnostics of inflammation in anatomically deep or optically dense tissues.