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.

Endothelial dysfunction and transcriptome aberration in mouse aortas induced by black phosphorus quantum dots and nanosheets.

Black phosphorus (BP) nanomaterials have shown great potential in versatile applications including biomedicine and potentially interact with vessel walls following intravenous injection in biomedical usage or environmental exposure. However, it remains unknown whether the exposure to BP nanomaterials induces alterations of the endothelium and further vascular injury. Herein, the endothelial function of human umbilical vein endothelial cells (HUVECs) and the structure and transcriptome of C57BL/6 mouse aortas are evaluated after the exposure to BP quantum dots (BPQDs) and nanosheets (BPNSs). BPNSs with irregular shapes and larger lateral size are more prone to inhibit in vitro angiogenesis at non-cytotoxic concentrations and markedly trigger platelet adhesion to HUVECs compared to BPQDs. Decreased nitric oxide (NO) production resulting from endothelial NO synthase (eNOS) dysregulation is involved in the BP-induced endothelial dysfunction. Both BPQDs and BPNSs at 0.8 and 6.4 µg mL-1 inhibit eNOS enzymatic activity through dephosphorylation of eNOS-Ser1177 and phosphorylation of eNOS-Thr495, but unlike BPQDs, BPNSs also downregulate eNOS expression. Despite no pathological damage in the structure of mouse aortas, BPQDs and BPNSs trigger aberration of aortic transcriptome involved in vasoconstriction abnormality, metabolic disturbance, and immune perturbation. This study demonstrates the adverse effect of BP nanomaterials on vasculature, and suggests that the morphological attribute of BP plays a crucial role in the vascular risks.