A versatile fabrication of upconversion nanophosphors with functional-surface tunable ligands

Rare earth upconversion nanophosphors (UCNPs) have been recognized as a promising new class of biological luminescent labels for fluorescence imaging. However, little work has been reported on the successful application of UCNPs in fluorescence imaging so far. The major problem with UCNPs arises from the difficulties in obtaining water-soluble UCNPs bearing appropriate surface functional groups. To solve this problem, herein we report a general procedure for the one-pot preparation of surface-functionalized UCNPs by a modified polyol route assisted by difunctional ligands containing a carboxyl group, such as 11-aminoundecanoic acid (ADA), poly(ethylene glycol) bis(carboxymethyl) ether (PEGBA) and folic acid (FA). The success of this one-pot method was confirmed by FT-IR and H-1 NMR spectroscopy. Due to the amino and carboxyl groups pointing outward, both amino-functionlized UCNPs (UCNPs-ADA) and carboxyl-functionlized UCNPs (UCNPs-PEGBA) are particularly suitable for coupling reactions with biological molecules and are potential candidates for bioimaging labels. By means of laser scanning upconversion luminescence microscopy, FA-functionlized UCNPs (UCNPs-FA) have been demonstrated to be effective in targeting folate-receptors overexpressing cancer cell lines. It is possible to design other surface-functionalized UCNPs by changing other bifunctional ligands with a carboxyl group. This strategy is general and facile for frabricating surface-functionalized UCNPs to potentially be used as bioimaging agents.