High-quality water-soluble and surface-functionalized upconversion nanocrystals as luminescent probes for bioimaging

Rare-earth upconversion nanophosphors (UCNPs) have great potential to become excellent biological luminescent labels for fluorescence bioimaging. However, it is still difficult to directly synthesize high-quality water-soluble UCNPs bearing appropriate functional groups using a one-step synthetic strategy. Herein, we report a one-step synthetic strategy for high-quality water-soluble and surface-functionalized UCNPs using a hydrothermal reaction assisted by binary cooperative ligands (HR-BCL). In this system, 6-aminohexanoic acid and oleate were introduced to control nuclear generation and crystal growth of small nanoparticles. The UCNPs synthesized here showed high crystalline and intense upconversion luminescence emission. Fourier-transform infrared and nuclear magnetic resonance spectroscopy indicated that 6-aminohexanoic acid and oleate cooperate as surface ligands to co-control the surface of UCNPs. Thus, the water-solubility of the as-prepared UCNPs can be tuned by changing the molar ratio of 6-aminohexanoic acid to oleate. The AA-modified UCNPs provided a free amine content of (6.0 ± 0.2) × 10−5 mol/g, which renders them dispersible in aqueous solution and allows further conjugation with folic acid (FA) for targeted bioimaging. Furthermore, the amine-functionalized UCNPs show intense near-infrared upconversion luminescence and were successfully applied in the lymphatic capillary bioimaging of small animals with a high signal-to-noise ratio, suggesting that these surface-functionalized UCNPs are promising candidates for luminescent biolabels.