Simultaneous synthesis and amine-functionalization of single-phase BaYF5:Yb/Er nanoprobe for dual-modal in vivo upconversion fluorescence and long-lasting X-ray computed tomography imaging

In this work, we developed a novel and biocompatible dual-modal nanoprobe based on single-phase amine-functionalized BaYF5:Yb/Er nanoparticles (NPs) for upconversion (UC) fluorescence and in vivo computed X-ray tomography (CT) bioimaging for the first time. High-quality water-soluble amine-functionalized BaYF5:Yb/Er NPs with an average size of 24 nm were synthesized by a facile environmentally friendly hydrothermal method for simultaneous synthesis and surface functionalization. Structure investigation based on the Rietveld refinement method revealed that the as-synthesized BaYF5:Yb/Er NPs present a cubic phase structure, which differs from the previously reported tetragonal structure. Under 980 nm excitation, high-contrast green and red UC emissions were observed from HeLa cells incubated with these amine-functionalized NPs. The UC spectra measured from the NPs incubated with HeLa cells presented only green and red UC emissions without any autofluorescence, further revealing that these NPs are ideal candidates for fluorescent bioimaging. In addition, the cell cytotoxicity test showed low cell toxicity of these NPs. These amine-functionalized NPs were also successfully used as CT agents for in vivo CT imaging because of the efficient X-ray absorption efficiency of Ba and doped Yb ions. A prolonged (2 h) signal enhancement of the spleen in a mouse was observed in CT imaging, which can improve the detection of splenic diseases. More importantly, the simultaneous X-ray and UC in vivo bioimaging was demonstrated in a nude mouse for the first time, indicating the as-prepared UCNPs can be successfully used as dual-modal bioprobes. These results demonstrate that BaYF5:Yb/Er NPs are ideal nanoprobes for dual-modal fluorescent/CT bioimaging with low cytotoxicity, non-autofluorescence, and enhanced detection of the spleen.