Impaired barrier integrity of endothelial cells induced by PEGylated black phosphorus nanosheets

Jiayan Chen; Weiwei Huan; Lijuan Mao; Meiling Huang; Yiqu Wu; Shulin Zhuang; Shixuan Cui

doi:10.1016/j.scitotenv.2022.160645

Impaired barrier integrity of endothelial cells induced by PEGylated black phosphorus nanosheets

Sci Total Environ. 2023 Feb 25:861:160645. doi: 10.1016/j.scitotenv.2022.160645. Epub 2022 Dec 2.

Authors

Jiayan Chen¹, Weiwei Huan², Lijuan Mao³, Meiling Huang⁴, Yiqu Wu⁴, Shulin Zhuang¹, Shixuan Cui⁵

Affiliations

¹ Key Laboratory of Environment Remediation and Ecological Health, Ministry of Education, College of Environmental and Resource Sciences, Zhejiang University, Hangzhou 310058, China; Women's Reproductive Health Key Laboratory of Zhejiang Province, Women's Hospital, School of Medicine, Zhejiang University, Hangzhou 310006, China.
² Zhejiang Provincial Key Laboratory of Chemical Utilization of Forestry Biomass, College of Chemistry and Materials Engineering, Zhejiang Agriculture and Forestry University, Hangzhou 311300, China.
³ Analysis Center of Agrobiology and Environmental Sciences, Faculty of Agriculture, Life and Environment Sciences (ACAES), Zhejiang University, Hangzhou 310058, China.
⁴ Key Laboratory of Environment Remediation and Ecological Health, Ministry of Education, College of Environmental and Resource Sciences, Zhejiang University, Hangzhou 310058, China.
⁵ Key Laboratory of Environment Remediation and Ecological Health, Ministry of Education, College of Environmental and Resource Sciences, Zhejiang University, Hangzhou 310058, China; Women's Reproductive Health Key Laboratory of Zhejiang Province, Women's Hospital, School of Medicine, Zhejiang University, Hangzhou 310006, China. Electronic address: sxcui@zju.edu.cn.

PMID: 36464060
DOI: 10.1016/j.scitotenv.2022.160645

Abstract

PEGylated black phosphorus nanosheets (PEG-BPNSs) have shown promising applications in biomedicine and potentially interact with the vasculature following iatrogenic exposures. Whether the exposure to PEG-BPNSs could induce toxic effects on endothelial cells that line the blood vessels remains largely unknown. Herein, we investigate the cellular response and transcriptional profiling of human umbilical vein endothelial cells (HUVECs) after the exposure to BPNSs and PEG-BPNSs. BPNSs and PEG-BPNSs induce cellular elongation and cause significant cytotoxicity to HUVECs at 0.8 μg/mL, with viabilities of 87.8% and 87.7% respectively. The transcriptome analysis indicates that BPNSs and PEG-BPNSs at 0.4 μg/mL cause marked alterations in the expression of genes associated with detection of stimulus, ion transmembrane transport and components of plasma membrane. BPNSs and PEG-BPNSs at 0.4 μg/mL decrease the transendothelial electrical resistance (TEER) across monolayers of HUVECs by 22.8% and 20.3% compared to the control, respectively. The disturbance of tight junctions (TJs) after 24 h exposure to 0.4 μg/mL BPNSs and PEG-BPNSs is indicated with the downregulated mRNA expression of zona occluden-1 (ZO-1) by respective 16.5% and 29.9%, which may be involved in the impairment of endothelial barrier integrity. Overall, the response of HUVECs to PEG-BPNSs and BPNSs has no statistical difference, suggesting that PEGylation does not attenuate the BPNSs-induced endothelial injury. This study demonstrates the detrimental effects of BPNSs and PEG-BPNSs on barrier integrity of HUVECs, contributing to our understanding on the potential toxicological mechanisms.

Keywords: Black phosphorus nanosheets; Endothelial barrier integrity; Human umbilical vein endothelial cells; PEGylation; Transcriptomics.

MeSH terms

Human Umbilical Vein Endothelial Cells
Humans
Nanostructures
Phosphorus*
Polyethylene Glycols* / toxicity

Substances

Phosphorus
Polyethylene Glycols