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

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.