Cell membrane-targeting NIR fluorescent probes with large Stokes shifts for ultralong-term transplanted neural stem cell tracking

There is an emerging therapeutic strategy to transplant stem cells into diseased host tissue for various neurodegenerative diseases, owing to their self-renewal ability and pluripotency. However, the traceability of long-term transplanted cells limits the further understanding of the mechanism of the therapy. Herein, we designed and synthesized a quinoxalinone scaffold-based near-infrared (NIR) fluorescent probe named QSN, which exhibits ultra-strong photostability, large Stokes shift, and cell membrane-targeting capacity. It could be found that QSN-labeled human embryonic stem cells showed strong fluorescent emission and photostability both in vitro and in vivo . Additionally, QSN would not impair the pluripotency of embryonic stem cells, indicating that QSN did not perform cytotoxicity. Moreover, it is worth mentioning that QSN-labeled human neural stem cells held cellular retention for at least 6 weeks in the mouse brain striatum post transplantation. All these findings highlight the potential application of QSN for ultralong-term transplanted cell tracking.