4.7 Article

Gold Nanoparticles Modified With Polyethyleneimine Disturbed the Activity of Drug-Metabolic Enzymes and Induced Inflammation-Mediated Liver Injury in Mice

期刊

FRONTIERS IN PHARMACOLOGY
卷 12, 期 -, 页码 -

出版社

FRONTIERS MEDIA SA
DOI: 10.3389/fphar.2021.706791

关键词

gold nanoparticles; drug-metabolic enzymes; hepatic transporters; cytochrome P450; liver inflammation

资金

  1. National Basic Research Program of China [2016YFA0201600]
  2. National Natural Science Foundation of China [11775234, 11975251, 11875268]
  3. Research Foundation of Guangzhou First People's Hospital [KY09040029]
  4. Open Project of Key Laboratory of Nanobiological Effects and Safety, CAS [NSKF202007]
  5. Xiejialin Foundation of IHEP [Y9546130U2]

向作者/读者索取更多资源

The study reveals that PEI-GNPs have significant effects on hepatic drug-metabolic enzymes and de novo lipogenesis in mice, leading to liver inflammation and partial hepatotoxicity. Therefore, it is crucial to consider the interaction between nanomaterials and the liver and modify the surface chemistry of GNPs before biomedical application.
Gold nanoparticles (GNPs) have been used as a potential bioactive platform for drug delivery due to their unique optical and thermal characteristics. Liver is the main organ in orchestrating physiological homeostasis through metabolization of drugs and detoxification of exogenous substances. Therefore, it is crucial to deeply understand the mechanism of nanoparticle-liver interaction and the potential hepatic effects of GNPs in vivo. In this study, we studied the hepatic impacts of the intravenously injected polyethyleneimine (PEI)-modified GNPs (PEI-GNPs) on the expression of hepatic drug-metabolic enzymes and sterol responsive element binding protein 1c (SREBP-1c)-mediated de novo lipogenesis in mice for 24 h and 1 week. PEI-GNP accumulation in the liver is associated with increased liver inflammation, as evidenced by the gene expression of pro-inflammatory cytokines. Moreover, the GNP-induced hepatotoxicity in mice is partly due to liver inflammation-triggered disruption in the function of drug-metabolic enzymes, including hepatic uptake and efflux transporters, cytochrome P450 (CYP450), and UDP-glucuronosyltransferases (UGTs). The study provides evidence that it is necessary to consider the nanomaterial-liver interaction and manipulate the surface chemistry of GNPs prior to biomedical application of nanoparticles.

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