Multifunctional nanoprobes based on upconverting lanthanide doped CaF2: towards biocompatible materials for biomedical imaging

Water dispersible Gd3+,Yb3+,Er3+ and Gd3+,Yb3+,Tm3+ doped CaF2 nanoparticles (NPs) were prepared by one-pot hydrothermal synthesis using citrate ions as capping agents without the need for any post-synthesis reaction. UC emissions are easily observed in the visible and infrared regions upon NIR diode laser excitation at 980 nm. EPR spectroscopy confirms the substitutional nature of the rare-earth doping, while magnetometric studies reveal that the NPs have a useful magnetization. MRI experiments conducted in vivo show that after 40 min from the injection, the NPs localize in the liver and spleen. Electron microscopy images of liver tissue reveal that the NPs are located in the Kupffer cells, although a small amount is also found in the hepatocytes. An excitation with a 980 nm emission on the excised liver and epithelial tissue induces clearly visible UC emission. The local temperature upon 980 nm irradiation was monitored in situ and it was found to increase slowly with the exposure time, maintaining under 1-2 °C for less than 60 second exposure. The NPs show a low toxicity towards cultured HeLa cells and human primary dendritic cells (DCs), and did not induce pro-inflammatory cytokine secretion by cultured human DCs, indicating that the NPs do not cause relevant adverse reactions in immune cells. Therefore, the present NPs are suitable candidates to be efficiently used in surgery applications, where spatial resolution and lack of harmful effects on human health are important issues.