Rational Design of Activatable Lanthanide NIR‐IIb Emissive Nanoprobe for In Situ Specific Imaging of HOCl In Vivo

Abstract Hypochlorous acid (HOCl), as an indispensable signaling molecule in organisms, is one of the key members of reactive oxygen species (ROS). However, in vivo, real‐time dynamic near‐infrared fluorescence imaging of HOCl levels in the 1400‐1700 nm sub‐window (NIR‐IIb) remains a major challenge due to the lack of suitable detection methods. Herein, a general design of HOCl‐responsive NIR‐IIb fluorescence nanoprobe is proposed by integrating NaLuF 4 Yb/Er@NaLuF 4 downshift nanoparticles (DSNPs) and HOCl recognition/NIR‐IIb emissive modulation unit of M 2‐x S (M = Cu, Co, Pb) nanodots for real‐time monitoring of HOCl levels. The fluorescence modulation unit of M 2‐x S nanodots presents remarkably enhanced absorption than Yb sensitizer at 980 nm and greatly inhibits the NIR‐IIb fluorescence emission via competitive absorption mechanism. While, the M 2‐x S nanodots are easily degraded after triggering by HOCl, resulting in HOCl responsive turn‐on (≈ten folds) NIR‐IIb emission at 1532 nm. More importantly, in vivo highly precise and specific monitoring of inflammatory with abnormal HOCl expression is successfully achieved. Thus, the explored competitive absorption mediated quenching‐activation mechanism provides a new general strategy of designing HOCl‐responsive NIR‐IIb fluorescence nanoprobe for highly specific and sensitive HOCl detection.