Acute hepatotoxicity of multimodal targeted imaging contrast agent NaLuF₄:Gd,Yb,Er-PEG/PEI-FA in mice

Abstract

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.

Recent advances in lanthanide-doped up-conversion probes for theranostics

“…Ln-UCNPs enter mice in tail vein injection and reach the whole body by blood circulation. Due to the high permeability effect of capillaries to nanoparticles, the liver and spleen become the main aggregate organs of Ln-UCNPs ( Li et al, 2017b ; Abualrejal et al, 2019 ; Chen et al, 2019 ; Guryev et al, 2019 ; Shan et al, 2020 ). Chen and co-workers designed targeted contrast agents modified by PEI and FA ( Chen et al, 2019 ).…”

“…Due to the high permeability effect of capillaries to nanoparticles, the liver and spleen become the main aggregate organs of Ln-UCNPs ( Li et al, 2017b ; Abualrejal et al, 2019 ; Chen et al, 2019 ; Guryev et al, 2019 ; Shan et al, 2020 ). Chen and co-workers designed targeted contrast agents modified by PEI and FA ( Chen et al, 2019 ). At 24 h and 18 days after the injection, the aggregation of nanoions in liver was higher than that in other tissues.…”