A high-performance cell-labeling NIR-II dye for in vivo cell tracking

Fluorescent dyes that emit in the second near-infrared (NIR-II, 1000–3000 nm) region have provided significant advances toward real-time and high-resolution imaging of vessel and lymphatic system. However, in vivo NIR-II tracking of the fate of labeled cells still remains challenging. Here, we develop a shielding unit–donor–acceptor–donor–shielding unit (S-D-A-D-S) NIR-II fluorophore (FE-4ZW) with zwitterionic terminal groups for high-efficiency cell labeling without using cell-penetrating peptides, which provides for enhanced non-invasive in vivo determination of the location of cell migration. The tethering terminal sulfoammonium inner salts are featured with its high affinity for cell membranes, thereby enabling the stable labeling even for fixed cells. The fate of transplanted stem cell and the tumor cell migration along lymphatic system in brain or periphery tissues are clearly monitored by the cell-internalized FE-4ZW. We also confirmed that a clinically used surfactant, D-α-tocopheryl polyethylene glycol-1000 succinate, can reduce the liver and spleen uptake of FE-4ZW. The fluorophore design strategy and cell-labeling technology reported here open a new realm in the visualization of cell migration and insight into the relocation process, thereby ultimately providing an opportunity to investigate in greater detail of the underlying mechanisms of stem cell therapy and tumor metastasis.