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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.
We appreciate financial support from National Natural Science Foundation of China (Nos. 21825402, 31400860, 21575096, and 21605109), Natural Science Foundation of Jiangsu Province of China (Nos. BK20191417 and BK20170061) and the Program for Jiangsu Specially-Appointed Professors to Prof. Yao He, a project funded by the Priority Academic Program Development of Jiangsu Higher Education Institutions (PAPD).