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表面涂层决定了磁铁矿纳米颗粒在小鼠肾足细胞和系膜细胞中的炎症潜能。

Surface coating determines the inflammatory potential of magnetite nanoparticles in murine renal podocytes and mesangial cells.

作者信息

Selc Michal, Razga Filip, Nemethova Veronika, Mazancova Petra, Ursinyova Monika, Novotova Marta, Kopecka Kristina, Gabelova Alena, Babelova Andrea

机构信息

Department of Nanobiology, Cancer Research Institute, Biomedical Research Center, Slovak Academy of Sciences Dubravska Cesta 9 84505 Bratislava Slovak Republic

Centre for Advanced Material Application, Slovak Academy of Sciences Dubravska Cesta 9 84511 Bratislava Slovak Republic.

出版信息

RSC Adv. 2020 Jun 23;10(40):23916-23929. doi: 10.1039/d0ra03133j. eCollection 2020 Jun 19.

Abstract

Drug-induced nephrotoxicity is a frequent adverse event and a dose-limiting factor in patient treatment and is a leading cause of prospective drug attrition during pharmaceutical development. Despite the obvious benefits of nanotherapeutics in healthcare strategies, the clearance of imaging agents and nanocarriers from the body following their therapeutic or diagnostic application generates concerns about their safety for human health. Considering the potency of nanoparticles and their massive utilization in biomedicine the impact of magnetic nanoparticles (MNPs) on cells forming the filtration apparatus of the kidney was studied. Using primary mouse renal glomerular podocytes and mesangial cells, we investigated their response to exposure to magnetic nanoparticles coated with polyethylene glycol and bovine serum albumin. Cultured podocytes were more sensitive to MNPs than mesangial cells displaying signs of cell damage and stronger inflammatory response. Both types of MNPs induced the remodeling of actin fibers, affected the cell shape and triggered expression of inflammatory cytokines TNFα and IL-6 in podocytes. On the other hand, iNOS was induced in both renal cell types but only by MNPs with a polyethylene glycol coating. Our results have revealed that the type of cell and the type of nanoparticle coating might be the strongest determinants of cellular response toward nanoparticle exposure. Differences in susceptibility of cells to MNPs might be evident also between neighboring renal cell subpopulations integrally forming functional sub-units of this organ.

摘要

药物性肾毒性是一种常见的不良事件,也是患者治疗中的剂量限制因素,并且是药物研发过程中药物前瞻性淘汰的主要原因。尽管纳米治疗剂在医疗保健策略中具有明显优势,但成像剂和纳米载体在治疗或诊断应用后从体内清除引发了人们对其对人类健康安全性的担忧。考虑到纳米颗粒的效力及其在生物医学中的大量应用,研究了磁性纳米颗粒(MNPs)对构成肾脏滤过装置的细胞的影响。使用原代小鼠肾小球足细胞和系膜细胞,我们研究了它们对暴露于涂有聚乙二醇和牛血清白蛋白的磁性纳米颗粒的反应。培养的足细胞对MNPs比系膜细胞更敏感,表现出细胞损伤迹象和更强的炎症反应。两种类型的MNPs均诱导肌动蛋白纤维重塑,影响细胞形状并触发足细胞中炎性细胞因子TNFα和IL-6的表达。另一方面,两种肾细胞类型均诱导了iNOS,但仅由涂有聚乙二醇的MNPs诱导。我们的结果表明,细胞类型和纳米颗粒涂层类型可能是细胞对纳米颗粒暴露反应的最强决定因素。在整体形成该器官功能亚单位的相邻肾细胞亚群之间,细胞对MNPs的敏感性差异也可能很明显。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/7581/9055089/f40a76bd5fd9/d0ra03133j-f1.jpg

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