A Novel NIR‐II Organic Fluorescent Small Molecule for the Early Diagnosis of Fat Embolism Syndrome

ABSTRACT Fat embolism syndrome (FES) is a serious complication following bone fracture, primarily resulting from the release of fat microparticles into circulation. Its diagnosis remains challenging due to the absence of specific imaging techniques and laboratory tests. Near‐infrared II (NIR‐II, 1000–1700 nm) fluorescence imaging (FI) has gained significant attention owing to its high tissue penetration and low background signal. While FI has been widely employed in basic research and clinical practice, its application in FES has not been explored. In this study, a NIR‐II organic fluorescent small molecule, FD‐1080‐C6, which exhibits fat affinity and viscosity responsiveness, is designed to enable FES diagnosis, for the first time. In the high‐viscosity microenvironment of FES, the lipophilic molecule FD‐1080‐C6, which possesses a donor–acceptor–donor (D–A–D) structure, undergoes restricted single‐bond rotation, promoting the formation of a rigid planar conformation and resulting in enhanced fluorescence intensity. In vitro evaluation confirms its responsiveness to lipid droplets, affinity for adipose tissue, and viscosity‐dependent fluorescence changes. Furthermore, its specificity for NIR‐II FI of FES is validated in the mouse. Additionally, FD‐1080‐C6 exhibits stable photothermal properties. FD‐1080‐C6 enables early diagnosis and longitudinal monitoring of disease progression in FES mice, offering a promising strategy for the management of FES.