Understanding the Role of the Lateral Dimensional Property of Graphene Oxide on Its Interactions with Renal Cells
文献类型：期刊论文
| 作者 | Chen, W; Wang, B ; Liang, SS; Wang, M; Zheng, LN; Xu, S; Wang, JL; Fang, H; Yang, P; Feng, WY
|
| 刊名 | MOLECULES
 |
| 出版日期 | 2022 |
| 卷号 | 27期号:22页码:7956 |
| 关键词 | graphene oxide lateral dimension renal cells interaction cytotoxicity |
| DOI | 10.3390/molecules27227956 |
| 文献子类 | Article |
| 英文摘要 | Renal excretion is expected to be the major route for the elimination of biomedically applied nanoparticles from the body. Hence, understanding the nanomedicine-kidney interaction is crucially required, but it is still far from being understood. Herein, we explored the lateral dimension- (similar to 70 nm and similar to 300 nm), dose- (1, 5, and 15 mg/kg in vivo and 0.1 similar to 250 mu g/mL in vitro), and time-dependent (48 h and 7 d in vivo) deposition and injury of PEGylated graphene oxide sheets (GOs) in the kidney after i.v. injection in mice. We specially investigated the cytotoxic effects on three typical kidney cell types with which GO renal excretion is related: human renal glomerular endothelial cells (HRGECs) and human podocytes, and human proximal tubular epithelial cells (HK-2). By using in vivo fluorescence imaging and in situ Raman imaging and spectroscopic analysis, we revealed that GOs could gradually be eliminated from the kidneys, where the glomeruli and renal tubules are their target deposition sites, but only the high dose of GO injection induced obvious renal histological and ultrastructural changes. We showed that the high-dose GO-induced cytotoxicity included a cell viability decrease and cellular apoptosis increase. GO uptake by renal cells triggered cellular membrane damage (intracellular LDH release) and increased levels of oxidative stress (ROS level elevation and a decrease in the balance of the GSH/GSSG ratio) accompanied by a mitochondrial membrane potential decrease and up-regulation of the expression of pro-inflammatory cytokines TNF-alpha and IL-18, resulting in cellular apoptosis. GO treatments activated Keap1/Nrf2 signaling; however, the antioxidant function of Nrf2 could be inhibited by apoptotic engagement. GO-induced cytotoxicity was demonstrated to be associated with oxidative stress and an inflammation reaction. Generally, the l-GOs presented more pronounced cytotoxicity and more severe cellular injury than s-GOs did, demonstrating lateral size-dependent toxicity to the renal cells. More importantly, GO-induced cytotoxicity was independent of renal cell type. The results suggest that the dosage of GOs in biomedical applications should be considered and that more attention should be paid to the ability of a high dose of GO to cause renal deposition and potential nephrotoxicity. |
| 电子版国际标准刊号 | 1420-3049 |
| 语种 | 英语 |
| WOS记录号 | WOS:000887424800001 |
| 源URL | [http://ir.ihep.ac.cn/handle/311005/299872]  |
| 专题 | 高能物理研究所_多学科研究中心 高能物理研究所_加速器中心 |
| 作者单位 | 中国科学院高能物理研究所 |
| 推荐引用方式 GB/T 7714 | Chen, W,Wang, B,Liang, SS,et al. Understanding the Role of the Lateral Dimensional Property of Graphene Oxide on Its Interactions with Renal Cells[J]. MOLECULES,2022,27(22):7956. |
| APA | Chen, W.,Wang, B.,Liang, SS.,Wang, M.,Zheng, LN.,...&Feng, WY.(2022).Understanding the Role of the Lateral Dimensional Property of Graphene Oxide on Its Interactions with Renal Cells.MOLECULES,27(22),7956. |
| MLA | Chen, W,et al."Understanding the Role of the Lateral Dimensional Property of Graphene Oxide on Its Interactions with Renal Cells".MOLECULES 27.22(2022):7956. |
入库方式： OAI收割
来源：高能物理研究所
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