NIR-II silver chalcogenide nanocrystals: synthesis, photophysical modulation and deep-tissue fluorescence imaging

Silver chalcogenide nanocrystals (Ag₂X NCs; X = S, Se, Te) have become an important class of low-toxicity emitters in the second near-infrared window (NIR-II, 1000-1700 nm). Recent progress in synthetic control, emission tuning, and surface engineering has significantly improved their brightness, stability, and suitability for biological use. This review provides a comprehensive overview of the development of Ag₂X NCs, focusing on synthetic methodologies and strategies for enhancing NIR-II fluorescence. We highlight their expanding applications in deep-tissue bioimaging, including vascular and lymphatic mapping, organ and skeletal visualization, targeted and activatable imaging, as well as emerging multiplexed and multimodal approaches. Finally, we critically examine current challenges and future directions, including clarifying emission mechanisms, improving scalable and environmentally friendly synthesis, optimizing surface chemistry for reliable biological interactions, enhancing quantitative imaging accuracy, and evaluating long-term biosafety. This review aims to support the continued improvement and biomedical translation of Ag₂X NCs as next-generation NIR-II probes.