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Fluorescein angiography (FA) is a standard imaging modality for evaluating vascular abnormalities in retina-related diseases, which is recognized as the major cause of vision loss. Long-term and real-time fundus angiography is of great importance in preclinical research, nevertheless remaining big challenges up to present. In this study, we demonstrate that long-term fluorescence imaging of retinal vessels is enabled through a kind of fluorescent nanoagents, which is made of small-sized (hydrodynamic diameter: ~ 3 nm) silicon nanoparticles (SiNPs) featuring strong fluorescence, robust photostability, lengthened blood residency and negligible toxicity. In particular, the presented SiNPs-based nanoagents are capable of imaging retinal capillaries in ~ 10 min, which is around 10-fold longer than that (~ 1 min) of fluorescein sodium (FS, known as the most widely used contrast agents for FA in clinic). Taking cynomolgus macaques as non-human primate-animal model, we further demonstrate the feasibility of real-time diagnosis of retinal diseases (e.g., age-related macular degeneration (AMD)) through dynamic monitoring of vascular dysfunction.
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