In vivo pharmacokinetics, transfer and clearance study of graphene oxide by La/Ce dual elemental labelling method

Abstract

Understanding the pharmacokinetics, distribution, and the behavior underlying the transfer and clearance of graphene oxide (GO) in vivo is critical for its clinical translation. However, GO is a single-atomic layered nanomaterial comprised only of carbon, hydrogen, and oxygen molecules, tracking GO in vivo is difficult. In this study, we developed a novel dual-element labelling strategy using the two rare-earth elements lanthanum (La) and cerium (Ce) as tags on polyvinylpyrrolidone (PVP) modified GO (La/Ce-GO-PVP) to successfully track the bioaccumulation, transfer, and clearance of GO in vivo. The data showed that intravenously injected La/Ce-GO-PVP nanosheets could be rapidly intercepted by the mononuclear phagocyte system rich organs (lung, liver, and spleen) and the kidney. A visual exploration for La/Ce-GO-PVP transfer and clearance in intra-organs and ultrastructure of the organs by laser ablation inductively coupled plasma mass spectrometry (LA-ICP-MS) and transmission electron microscopy (TEM) was performed. The thin, flexible, and well-dispersed GO-PVP was observed to enter into the deep sub-organs of the lung, liver and spleen, pass through the glomerular filtration barrier (GFB) of the kidney and was excreted in the urine. In addition, we observed the GO nanosheets by rolling, crumpling or folding their morphology to facilitate their transfer across the continuous, fenestrated, and discontinuous endothelium, where GO can then be transferred and cleared in the intra-organs. This study provides a further understanding for the thin and flexible GO transfer and clearance in vivo, and the interactions with physiological barriers in view of their potential biomedical applications.