Fluorescence Resonance Energy Transfer Mediated Large Stokes Shifting Near-Infrared Fluorescent Silica Nanoparticles for in Vivo Small-Animal Imaging

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Fluorescent dye-doped silica nanoparticles are increasingly used for in vivo imaging due to their unique biocompatibility and easy surface modification. However, the utility of existing fluorescent dye-doped silica nanoparticles for in vivo imaging is still limited because most studies are focused on doping single near-infrared (NIR) dyes in the silica matrix, which would cause background and crosstalk between the excitation light and the emitting signals due to the small Stokes shift of the traditional NIR dyes. To address this issue, we present a novel large Stokes shifting NIR fluorescent silica nanoparticles (LSS-NFSiNPs) based on the principle of fluorescence resonance energy transfer. Two highly water-soluble dyes, tris(2,2-bipyridyl)dichlororuthenium(II) hexahydrate (RuBpy) and methylene blue (MB), were chose as the model donor-acceptor pair. The LSS-NFSiNPs were prepared by synchronously doping RuBpy and MB in the silica nanoparticles. By optimizing the molar ratio of RuBpy and MB for doping in the silica nanoparticles, the energy transfer from RuBpy to MB occurred in the silica matrix, resulting in a near-infrared fluorescent silica nanoparticles with strong fluorescence and large Stokes shift (>200 nm). As a result, it can effectively help to increase the discrimination of fluorescence signal of interest over other background signals. With a combination of excellent stability, large Stokes shift, and near-infrared spectral properties, this novel LSS-NFSiNPs provides real-time, deep-tissue fluorescent imaging of live animals. More importantly, the LSS-NFSiNPs can also be gradually cleared from the body through the urinary clearance system. We anticipate this design concept can lay a foundation for further development of in vivo optical nanoparticulate contrast toward clinical applications.