Biodistribution and pulmonary toxicity of intratracheally instilled graphene oxide in mice

Abstract

Graphene and its derivatives (for example, nanoscale graphene oxide (NGO)) have emerged as extremely attractive nanomaterials for a wide range of applications, including diagnostics and therapeutics. In this work, we present a systematic study on the in vivo distribution and pulmonary toxicity of NGO for up to 3 months after exposure. Radioisotope tracing and morphological observation demonstrated that intratracheally instilled NGO was mainly retained in the lung. NGO could result in acute lung injury (ALI) and chronic pulmonary fibrosis. Such NGO-induced ALI was related to oxidative stress and could effectively be relieved with dexamethasone treatment. In addition, we found that the biodistribution of 125I-NGO varied greatly from that of 125I ions, hence it is possible that nanoparticulates could deliver radioactive isotopes deep into the lung, which might settle in numerous ‘hot spots’ that could result in mutations and cancers, raising environmental concerns about the large-scale production of graphene oxide. The remarkable physical properties of graphene and its derivatives suggest myriad potential uses for these carbon-based nanomaterials, such as drug delivery vehicles. To assess the potential safety issues surrounding their biomedical use, a team led by Chunhai Fan at the Shanghai Institute of Applied Physics in China examined the distribution and toxicity of nanoscale graphene oxide (NGO) in mice. The researchers labelled NGO flakes with a radioisotope of iodine (125I) to trace their distribution in the animals following exposure by inhalation. Over the course of the three-month trial, 125I–NGO was found to have been largely retained in the lung, where it caused dose-dependent acute lung injury and chronic pulmonary lesions. Furthermore, the distribution of 125I–NGO was found to be different to that of 125I ions. This raises the possibility that inhaled NGO may ferry adsorbed radioactive species deep into the lung, highlighting the need to investigate its potential risks to human health and to optimize the flakes' dimensions to minimize their toxicity. Nanoscale graphene oxide (NGO) has emerged as extremely attractive nanomaterials for diagnostics and therapeutics. In this work, we present a systematic study on the in vivo distribution and pulmonary toxicity of NGO for up to 3 months after exposure. Radioisotope tracing and morphological observation demonstrated that intratracheally instilled NGO was mainly retained in the lung. NGO could result in acute lung injury (ALI) and chronic pulmonary fibrosis, which raises environmental concerns about the large-scale production of graphene oxide. Nevertheless, we also noted that the NGO-induced ALI was related to oxidative stress and could effectively be relieved with dexamethasone treatment.