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库普弗细胞通过红细胞吞噬作用将 C 标记的少层石墨烯降解为 CO 在肝脏中。

Kupffer Cells Degrade C-Labeled Few-Layer Graphene to CO in Liver through Erythrophagocytosis.

机构信息

State Key Laboratory of Pollution Control and Resource Reuse, School of the Environment, Nanjing University, Nanjing 210093, China.

Division of NanoMedicine, Department of Medicine, Centre for Environmental Implications of Nanotechnology, University of California, Los Angeles, Los Angeles, California 90095, United States.

出版信息

ACS Nano. 2021 Jan 26;15(1):396-409. doi: 10.1021/acsnano.0c07452. Epub 2020 Nov 5.

DOI:10.1021/acsnano.0c07452
PMID:33150787
Abstract

The distribution and clearance of graphene materials as drug delivery systems at organ and suborgan levels over the long term remain unclear. Here we compared the fate of C-labeled few-layer graphene with different lateral sizes in mice after one intravenous injection for up to 1 year and demonstrated that few-layer graphene mainly accumulated in the liver, and larger graphene can be degraded into CO by Kupffer cells. The mechanism involves the uptake of graphene by liver cells, larger graphene-induced membrane perturbation of red blood cells, and enhanced erythrophagocytosis by the Kupffer cells, resulting in the degradation of hemoglobin into hemes and a rise in iron concentrations in cells. The increased iron triggered a Fenton reaction to generate the hydroxyl radical, facilitating the degradation of larger graphene into CO. Our findings propose a mechanism for the transformation of graphene that significantly contributes to our understanding of the hepatic fate of graphene .

摘要

石墨烯作为药物输送系统在器官和亚器官水平的分布和清除长期以来仍不清楚。在这里,我们比较了在长达 1 年的时间内,经过一次静脉注射后,不同侧向尺寸的 C 标记的少层石墨烯在小鼠体内的命运,并证明少层石墨烯主要在肝脏中积累,而较大的石墨烯可以被库普弗细胞降解为 CO。该机制涉及肝细胞对石墨烯的摄取、较大石墨烯对红细胞膜的干扰以及库普弗细胞增强的红细胞吞噬作用,导致血红蛋白降解为血红素和细胞中铁浓度升高。增加的铁触发芬顿反应产生羟基自由基,促进较大石墨烯降解为 CO。我们的发现提出了一种石墨烯转化的机制,这对我们理解石墨烯在肝脏中的命运有重要贡献。

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