Synthesis, characterization, and in vivo targeted imaging of amine-functionalized rare-earth up-converting nanophosphors

Rare-earth up-converting nanophosphors (UCNPs) have great potential to become a new generation of biological luminescent labels, but their use has been limited by difficulties in obtaining water-soluble UCNPs bearing appropriate functional groups. To address this problem, we report herein a simple and efficient procedure for the preparation of amine-functionalized UCNPs by a modified hydrothermal microemulsion route assisted with 6-aminohexanoic acid. The amine content of the resultant UCNPs has been determined to be (9.5 ± 0.8) × 10−5 mol/g, which not only confers excellent dispersibility in aqueous solution, but also allows further conjugation with targeted molecules such as folic acid (FA) as a ligand. By means of the laser scanning up-conversion luminescence microscopy (LSUCLM) and the in vivo up-conversion luminescence (UCL) imaging under excitation at the CW infrared laser at 980 nm, FA-coupled UCNPs have been demonstrated to be effective in targeting folate-receptor overexpressing HeLa cells in vitro and HeLa tumor in vivo and ex vivo. These results indicated that our UCNPs could be used as whole-body targeted UCL imaging agents.