Water-dispersible, pH-stable and highly-luminescent organic dye nanoparticles with amplified emissions for in vitro and in vivo bioimaging.

A new strategy is presented for using doped small-molecule organic nanoparticles (NPs) to achieve high-performance fluorescent probes with strong brightness, large Stokes shifts and tunable emissions for in vitro and in vivo imaging. The host organic NPs are used not only as carriers to encapsulate different doped dyes, but also as fluorescence resonance energy transfer donors to couple with the doped dyes (as acceptors) to achieve multicolor luminescence with amplified emissions (AE). The resulting optimum green emitting NPs show high brightness with quantum yield (QY) of up to 45% and AE of 12 times; and the red emitting NPs show QY of 14% and AE of 10 times. These highly-luminescent doped NPs can be further surface modified with poly(maleic anhydride-alt-1-octadecene)-polyethylene glycol (C18PMH-PEG), endowing them with excellent water dispersibility and robust stability in various bio-environments covering wide pH values from 2 to 10. In this study, cytotoxicity studies and folic acid targeted cellular imaging of these multicolor probes are carried out to demonstrate their potential for in vitro imaging. On this basis, applications of the NP probes in in vivo and ex vivo imaging are also investigated. Intense fluorescent signals of the doped NPs are distinctly, selectively and spatially resolved in tumor sites with high sensitivity, due to the preferential accumulation of the NPs in tumor sites through the passive enhanced permeability and retention effect. The results clearly indicate that these doped NPs are promising fluorescent probes for biomedical applications.