Activatable Near-Infrared Fluorescent Probes for Immune Cell Imaging

Immune cell therapy has emerged as a highly promising modality in cancer immunotherapy. Effective in vivo cell tracking is essential for the real-time assessment of cell distribution, viability, and proliferation, providing critical insights into both fundamental research and clinical translation. However, conventional fluorescence imaging often suffers from limited sensitivity due to high background signals and poor tissue penetration. Consequently, activatable near-infrared (NIR) fluorescence imaging has garnered significant attention. By leveraging the NIR window to minimize tissue attenuation and autofluorescence, these probes offer superior depth penetration. Unlike "always-on" probes that generate nonspecific background noise, activatable probes remain quenched until triggered by specific biomarkers, thereby substantially improving the signal-to-noise ratio. This review summarizes key activation mechanisms and synthetic strategies for these probes, highlighting their application in immune cell monitoring. We also discuss current challenges, such as identifying molecular targets, and envision that advancing activatable NIR probes will play a pivotal role in optimizing clinical immunotherapy.