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一年后暴露于 C-少层石墨烯在小鼠中的生物分布评估:单次和重复气管内给药。

One-year post-exposure assessment of C-few-layer graphene biodistribution in mice: single repeated intratracheal administration.

机构信息

Université Paris Saclay, CEA, INRAE, Département Médicaments et Technologies pour la Santé (DMTS), SCBM, 91191 Gif-sur-Yvette, France.

Université Paris Saclay, CEA, INRAE, Département Médicaments et Technologies pour la Santé (DMTS), SIMos, 91191 Gif-sur-Yvette, France.

出版信息

Nanoscale. 2023 Nov 9;15(43):17621-17632. doi: 10.1039/d3nr03711h.

Abstract

Research on graphene-based nanomaterials has experienced exponential growth in the last few decades, driven by their unique properties and their future potential impact on our everyday life. With the increasing production and commercialization of these materials, there is significant interest in understanding their fate . Herein, we investigated the distribution of C-few-layer graphene (C-FLG) flakes (lat. dim. ∼ 500 nm) in mice over a period of one year. Furthermore, we compared the effects of repeated low-dose and acute high-dose exposure by tracheal administration. The results showed that most of the radioactivity was found in the lungs in both cases, with longer elimination times in the case of acute high-dose administration. In order to gain deeper insights into the distribution pattern, we conducted investigations using μ-autoradiography on tissue sections, revealing the heterogeneous distribution of the material following administration. For the first time, μ-autoradiography was used to conduct a comprehensive investigation into the distribution and potential presence of FLG within lung cells isolated from the exposed lungs. The presence of radioactivity in lung cells strongly suggests internalization of the C-FLG particles. Overall these results show the long-term accumulation of the material in the lungs over one year, regardless of the administration protocol, and the higher biopersistence of FLG in the case of an acute exposure. These findings highlight the importance of the exposure scenario in the context of intratracheal administration, which is of interest in the evaluation of the potential health risks of graphene-based nanomaterials.

摘要

在过去的几十年中,由于其独特的性质和对我们日常生活的未来潜在影响,基于石墨烯的纳米材料的研究呈指数级增长。随着这些材料的产量和商业化的增加,人们对了解它们的命运产生了浓厚的兴趣。在此,我们研究了 C-少层石墨烯 (C-FLG) 薄片(长径比约 500nm)在一年时间内在小鼠体内的分布情况。此外,我们还比较了经气管给药时重复低剂量和急性高剂量暴露的影响。结果表明,在两种情况下,大多数放射性物质都在肺部,急性高剂量给药的清除时间更长。为了更深入地了解分布模式,我们对组织切片进行了μ自显影研究,结果表明,在给药后,材料的分布呈异质性。首次使用μ自显影术对从暴露肺部分离的肺细胞中 FLG 的分布和潜在存在进行了全面研究。肺细胞中存在放射性物质强烈表明 C-FLG 颗粒已被内化。这些结果表明,无论给药方案如何,该材料在一年内都会在肺部长期积累,并且在急性暴露时 FLG 的生物持久性更高。这些发现强调了在气管内给药的情况下,暴露情况的重要性,这对于评估基于石墨烯的纳米材料的潜在健康风险具有重要意义。

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