Simultaneous Deep Tracking of Stem Cells by Surface Enhanced Raman Imaging Combined with Single‐Cell Tracking by NIR‐II Imaging in Myocardial Infarction

Abstract Stem cell therapy has been used as a potential approach for the treatment of myocardial infarction (MI) over the last two decades. Imaging cellular behaviors of the transplanted stem cells with deep tissue penetration and high precision imaging modalities is crucial for the clinical translation of stem cell therapy approaches for MI. Herein, a gold nanostar (Au‐Star) based second near‐infrared window (NIR‐II) fluorescence/surface enhanced Raman scattering dual‐modal imaging probe (gold nanostar‐3.3′‐diethylthiatricarbocyanine iodide‐silver sulfide nanoparticles, Au‐Star‐DTTC‐Ag₂S NPs, GDS NPs) is designed for labeling and precise tracking of the stem cells. The Ag₂S compartment generates strong NIR‐II emission, which compensates for the deficiencies of bioluminescent imaging and enables the dynamic observation of in vivo cellular behavior. Subsequently, the specific Raman signal of Au‐Star‐DTTC compartment enables high‐resolution imaging, which could effectively delineate stem cells from the surrounding normal tissues, even at a single‐cell resolution. Using this imaging and tracking approach, it is able to track stem cells in hypodermic and MI models, with high resolution and depth‐independent imaging capabilities, which have not been reported in any other cell tracking platform. This two‐armed imaging toolkit offers new opportunities for a wide range of mechanistic stem cell therapy investigations in different organs.