In the past few decades, upconversion nanoparticles (abbreviated as UCNPs) have been more widely applied in the biomedical fields, such as in vitro and in vivo upconversion fluorescent bioimaging, photodynamic therapy, biological macromolecular detection, imaging mediated drug delivery and so on. But meanwhile, there is still not much research on the acute toxicity of upconversion nanoparticles in vivo, such as acute hepatotoxicity. In this work, we studied the in vivo biodistribution and acute hepatotoxicity of multimodal targeted contrast agent NaLuF 4 :Gd,Yb,Er-PEG/PEI-FA nanoprobe, which were synthesized by the solvothermal method and modified with Polyethylene glycol (PEG), Polyetherimide (PEI), folic acid (FA) on the surface. The acute hepatotoxicity in mice was systematically assessed after tail vein injection of different concentration of UCNPs. The results showed that NaLuF 4 :Gd,Yb,Er-PEG/ PEI-FA nanoparticles with an average diameter of 44.5 ± 10.4 nm, and three typical upconversion fluorescence emission bands at 520 nm, 540 nm and 660 nm under the excitation of 980 nm laser. In vivo distribution experiments results demonstrated that approximately 87% of UCNPs injected through the tail vein accumulate in the liver. In the acute hepatotoxicity test, the intravenously injection dose of UCNPs was 10, 40, 70 and 100 mg/kg, respectively. The body weight, blood routine, serum biochemistry, histomorphology and liver oxidative stress were detected and observed no significant acute hepatotoxicity damage under the injection dose of 100 mg/kg. In conclusion, NaLuF 4 :Gd,Yb,Er-PEG/PEI-FA nanoprobes are safe and reliable, and have potential applications in the field of tumor targeted multimodal imaging.

Cerium oxide (CeO2) nanoparticles have unique redox properties and exert excellent antioxidant effects in the biological environment. In recent years, many researchers have focused on the CeO2 nanoparticles as an effective antioxidant drug in the prevention and treatment of various diseases. However, the toxicity of CeO2 nanoparticles in vivo remains controversial and still needs intensive research. Therefore, the objective of this study is to investigate the pulmonary and systemic toxicity in rats after 14 days of exposure to the PEGylated CeO2 nanoparticles (abbreviated as CNPs; exposure dose of 2, 10, or 20 mg/kg) through a single intratracheal instillation (IT). We assessed the indicators of lung injury and the pathological damage degree of lung tissue. The bronchoalveolar lavage fluid (BALF) analysis and lung histopathology revealed the occurrence of slight pulmonary inflammation in the 20‐mg/kg experimental group rats. However, the inflammation factors in the lung tissue of every group rats did not significantly increase, and the levels of superoxide dismutase (SOD) and glutathione (GSH) in lung tissue homogenate rose considerably in the experimental groups. Collectively, these results indicated that pulmonary exposure by the high dose of CNPs could induce mild pulmonary inflammation but did not cause severe systemic toxicity. Moreover, we speculate that the mechanism of pulmonary toxicity of CNPs in rats was due to the autophagic death of healthy lung epithelial cells mediated by endoplasmic reticulum stress. Our results implicate that CNPs can be safely used as an antioxidant drug for the oxidative stress pulmonary diseases.