Elemental bio-imaging of PEGylated NaYF4:Yb/Tm/Gd upconversion nanoparticles in mice by laser ablation inductively coupled plasma mass spectrometry to study toxic side effects on the spleen, liver and kidneys.

Rare-earth upconversion nanoparticles (UCNPs) are considered stable nanoprobes with low toxicity and deep tissue penetration. However, the increasing use of UCNPs has raised concerns about their potential toxicity in living organisms. Very few studies have reported the toxicity of UCNPs; hence, it is not possible to conclude yet that UCNPs are safe. In this study, the distribution of PEGylated NaYF4: Yb/Tm/Gd nanoparticles (PEG-UCNPs) in female Balb/c mice following intravenous administration, and imaging in the spleen, liver and kidney was examined by laser ablation inductively coupled plasma mass spectrometry (LA-ICP-MS). PEG-UCNPs distributed primarily to the liver and spleen, with significant but lower levels being noted in the kidneys, heart, and lungs. At the sub-organ level, PEG-UCNPs mainly accumulated within the red pulp of the spleen instead of the white pulp, which indicated that PEG-UCNPs are poorly immunogenic, or not immunogenic at all. The imaging of Cu in the liver and spleen showed that the primary clearance organ for PEG-UCNPs is the liver, although they are accumulated in the spleen rather than the liver. This can be explained by the fact that excess superoxide anions produced by phagocytosis of the PEG-UCNPs need Cu-Zn-superoxide dismutase to be converted to hydrogen peroxide. From the Fe, Cu, and Zn imaging of the kidney, it was concluded that PEG-UCNPs do not exhibit nephrotoxicity.