Multifaceted Characterization for the Hepatic Clearance of Graphene Oxide and Size-Related Hepatic Toxicity

Understanding the final fate of nanomaterials (NMs) in the liver is crucial for their safer application. As a representative two-dimensional (2D) soft nanomaterial, graphene oxide (GO) has shown to have high potential for applications in the biomedical field, including in biosensing, drug delivery,...

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Main Authors: Zongyi Su, Wei Chen, Shanshan Liang, Hao Fang, Minglu Zhang, Meng Wang, Lingna Zheng, Bing Wang, Yi Bi, Weiyue Feng
Format: Article
Language:English
Published: MDPI AG 2024-03-01
Series:Molecules
Subjects:
Online Access:https://www.mdpi.com/1420-3049/29/6/1335
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author Zongyi Su
Wei Chen
Shanshan Liang
Hao Fang
Minglu Zhang
Meng Wang
Lingna Zheng
Bing Wang
Yi Bi
Weiyue Feng
author_facet Zongyi Su
Wei Chen
Shanshan Liang
Hao Fang
Minglu Zhang
Meng Wang
Lingna Zheng
Bing Wang
Yi Bi
Weiyue Feng
author_sort Zongyi Su
collection DOAJ
description Understanding the final fate of nanomaterials (NMs) in the liver is crucial for their safer application. As a representative two-dimensional (2D) soft nanomaterial, graphene oxide (GO) has shown to have high potential for applications in the biomedical field, including in biosensing, drug delivery, tissue engineering, therapeutics, etc. GO has been shown to accumulate in the liver after entering the body, and thus, understanding the GO–liver interaction will facilitate the development of safer bio-applications. In this study, the hepatic clearance of two types of PEGylated GOs with different lateral sizes (<i>s</i>-GOs: ~70 nm and <i>l</i>-GOs: ~300 nm) was carefully investigated. We found that GO sheets across the hepatic sinusoidal endothelium, which then may be taken up by the hepatocytes via the Disse space. The hepatocytes may degrade GO into dot-like particles, which may be excreted via the hepatobiliary route. In combination with ICP-MS, LA-ICP-MS, and synchrotron radiation FTIR techniques, we found that more <i>s</i>-GO sheets in the liver were prone to be cleared via hepatobiliary excretion than <i>l</i>-GO sheets. A Raman imaging analysis of I<sub>D</sub>/I<sub>G</sub> ratios further indicated that both <i>s</i>-GO and <i>l</i>-GO generated more defects in the liver. The liver microsomes may contribute to GO biotransformation into O-containing functional groups, which plays an important role in GO degradation and excretion. In particular, more small-sized GO sheets in the liver were more likely to be cleared via hepatobiliary excretion than <i>l</i>-GO sheets, and a greater clearance of <i>s</i>-GO will mitigate their hepatotoxicity. These results provide a better understanding of the hepatic clearance of soft NMs, which is important in the safer-by-design of GO.
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spelling doaj.art-53fca334fc85413980a730a2a47b81082024-03-27T13:57:05ZengMDPI AGMolecules1420-30492024-03-01296133510.3390/molecules29061335Multifaceted Characterization for the Hepatic Clearance of Graphene Oxide and Size-Related Hepatic ToxicityZongyi Su0Wei Chen1Shanshan Liang2Hao Fang3Minglu Zhang4Meng Wang5Lingna Zheng6Bing Wang7Yi Bi8Weiyue Feng9School of Pharmacy, Key Laboratory of Molecular Pharmacology and Drug Evaluation (Yantai University), Ministry of Education, Collaborative Innovation Center of Advanced Drug Delivery System and Biotech Drugs in Universities of Shandong, Yantai University, Yantai 264005, ChinaCAS Key Laboratory for Biomedical Effects of Nanomaterials and Nanosafety, Institute of High Energy Physics, Chinese Academy of Sciences, Beijing 100049, ChinaCAS Key Laboratory for Biomedical Effects of Nanomaterials and Nanosafety, Institute of High Energy Physics, Chinese Academy of Sciences, Beijing 100049, ChinaCAS Key Laboratory for Biomedical Effects of Nanomaterials and Nanosafety, Institute of High Energy Physics, Chinese Academy of Sciences, Beijing 100049, ChinaCAS Key Laboratory for Biomedical Effects of Nanomaterials and Nanosafety, Institute of High Energy Physics, Chinese Academy of Sciences, Beijing 100049, ChinaCAS Key Laboratory for Biomedical Effects of Nanomaterials and Nanosafety, Institute of High Energy Physics, Chinese Academy of Sciences, Beijing 100049, ChinaCAS Key Laboratory for Biomedical Effects of Nanomaterials and Nanosafety, Institute of High Energy Physics, Chinese Academy of Sciences, Beijing 100049, ChinaCAS Key Laboratory for Biomedical Effects of Nanomaterials and Nanosafety, Institute of High Energy Physics, Chinese Academy of Sciences, Beijing 100049, ChinaSchool of Pharmacy, Key Laboratory of Molecular Pharmacology and Drug Evaluation (Yantai University), Ministry of Education, Collaborative Innovation Center of Advanced Drug Delivery System and Biotech Drugs in Universities of Shandong, Yantai University, Yantai 264005, ChinaCAS Key Laboratory for Biomedical Effects of Nanomaterials and Nanosafety, Institute of High Energy Physics, Chinese Academy of Sciences, Beijing 100049, ChinaUnderstanding the final fate of nanomaterials (NMs) in the liver is crucial for their safer application. As a representative two-dimensional (2D) soft nanomaterial, graphene oxide (GO) has shown to have high potential for applications in the biomedical field, including in biosensing, drug delivery, tissue engineering, therapeutics, etc. GO has been shown to accumulate in the liver after entering the body, and thus, understanding the GO–liver interaction will facilitate the development of safer bio-applications. In this study, the hepatic clearance of two types of PEGylated GOs with different lateral sizes (<i>s</i>-GOs: ~70 nm and <i>l</i>-GOs: ~300 nm) was carefully investigated. We found that GO sheets across the hepatic sinusoidal endothelium, which then may be taken up by the hepatocytes via the Disse space. The hepatocytes may degrade GO into dot-like particles, which may be excreted via the hepatobiliary route. In combination with ICP-MS, LA-ICP-MS, and synchrotron radiation FTIR techniques, we found that more <i>s</i>-GO sheets in the liver were prone to be cleared via hepatobiliary excretion than <i>l</i>-GO sheets. A Raman imaging analysis of I<sub>D</sub>/I<sub>G</sub> ratios further indicated that both <i>s</i>-GO and <i>l</i>-GO generated more defects in the liver. The liver microsomes may contribute to GO biotransformation into O-containing functional groups, which plays an important role in GO degradation and excretion. In particular, more small-sized GO sheets in the liver were more likely to be cleared via hepatobiliary excretion than <i>l</i>-GO sheets, and a greater clearance of <i>s</i>-GO will mitigate their hepatotoxicity. These results provide a better understanding of the hepatic clearance of soft NMs, which is important in the safer-by-design of GO.https://www.mdpi.com/1420-3049/29/6/1335graphene oxidehepatic clearancemultifaceted characterization
spellingShingle Zongyi Su
Wei Chen
Shanshan Liang
Hao Fang
Minglu Zhang
Meng Wang
Lingna Zheng
Bing Wang
Yi Bi
Weiyue Feng
Multifaceted Characterization for the Hepatic Clearance of Graphene Oxide and Size-Related Hepatic Toxicity
Molecules
graphene oxide
hepatic clearance
multifaceted characterization
title Multifaceted Characterization for the Hepatic Clearance of Graphene Oxide and Size-Related Hepatic Toxicity
title_full Multifaceted Characterization for the Hepatic Clearance of Graphene Oxide and Size-Related Hepatic Toxicity
title_fullStr Multifaceted Characterization for the Hepatic Clearance of Graphene Oxide and Size-Related Hepatic Toxicity
title_full_unstemmed Multifaceted Characterization for the Hepatic Clearance of Graphene Oxide and Size-Related Hepatic Toxicity
title_short Multifaceted Characterization for the Hepatic Clearance of Graphene Oxide and Size-Related Hepatic Toxicity
title_sort multifaceted characterization for the hepatic clearance of graphene oxide and size related hepatic toxicity
topic graphene oxide
hepatic clearance
multifaceted characterization
url https://www.mdpi.com/1420-3049/29/6/1335
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