Atomically Precise Metal Clusters for NIR-II Imaging.

ConspectusNear-infrared II (NIR-II, 1000-3000 nm), also defined as shortwave infrared (SWIR) imaging, offers reduced light scattering and low tissue absorption, enabling centimeter-scale penetration and high signal-to-noise ratios. It has become a powerful tool for fundamental biomedical research and clinicopathological diagnosis. Metal clusters, with their discrete, molecule-like electronic structures, exhibit exceptional NIR-II luminescence. Notably, atomically precise clusters with well-defined three-dimensional coordination allow fine-tuning of NIR-II optical properties through atomic engineering, ligand design, and surface modification. Their ultrasmall (∼2 nm) size further supports efficient renal clearance, low toxicity, and excellent biocompatibility, highlighting their promise for clinical translation. Moreover, coupling metal clusters with advanced NIR-II imaging technologies and artificial intelligence enables high-resolution, deep-tissue visualization with enhanced sensitivity and accuracy. Therefore, achieving high-performance biomedical imaging and fulfilling clinical needs require a comprehensive understanding of the luminescence mechanisms of serial atomically precise clusters and their corresponding microscopic imaging methods, together with the parallel development of dedicated artificial-intelligence tools to fully unlock their application potential.In this Account, we summarize the NIR-II luminescence properties, imaging techniques, biomedical applications, and biosafety of atomically precise metal clusters. We begin by presenting their crystal structures, as a clear understanding of atomic arrangements is essential for precise property control. We then outline key photophysical parameters, emission wavelength, and quantum yield (QY), followed by NIR-II luminescence mechanisms and strategies for their rational tailoring, which underpin the design of next-generation imaging probes. We further highlight the synergistic integration of metal clusters with advanced imaging technology, enabling high signal-to-noise imaging of disease progression and spatially resolved phenotyping of pathological tissue. This section includes wide-field imaging, three-dimensional microscopy imaging, and emerging artificial intelligence assisted image processing. We next examine major NIR-II biomedical applications, including tumor progression, neurological imaging, and clinical pathology visualization, and other lesions imaging associated with diverse diseases. Finally, we evaluate the biosafety of metal clusters, focusing on the effects of size, surface chemistry and renal clearance, to inform their safe and effective clinical translation.This Account presents the fundamental physics and NIR-II luminescence of atomically precise metal clusters, detailing their emission wavelengths, QYs, luminescence mechanisms, and tuning strategies. Coupling these clusters with advanced imaging technology and deep learning enables high-resolution imaging with markedly enhanced signal-to-noise ratios. Their excellent biocompatibility allows dynamic monitoring of pathological progression in major diseases, including cardiovascular, cerebrovascular, and malignant tumors at micrometer to submicrometer scales, while supporting intraoperative navigation and localized, site-specific targeting for clinical translation.