LAUSR

Abstract Along with its wide range of potential applications, human exposure to mesoporous tantalum oxide nanomaterials (PEG@mTa2O5) has substantially risen. Accumulative toxic investigations have shown the PEG@mTa2O5 intake and cardiovascular diseases (CVD). Endothelial cell death is crucial in the onset and development of atherosclerosis. Still, the molecular mechanism connecting PEG@mTa2O5 and endothelium apoptosis remains unclear. Herein, we studied the absorption and toxic action of mesoporous tantalum oxide (mTa2O5) nanomaterials with polyethylene glycol (PEG) utilizing human cardio microvascular endothelial cells (HCMECs). We also showed that PEG@mTa2O5 promoted apoptosis in endothelial cells using flow cytometry and AO-EB staining. In conjunction with the ultrastructure modifications, PEG@mTa2O5 prompted mitochondrial ROS production, cytosolic Ca2+ overload, ΔΨm collapse, and ER stress verified by elevated ER-Tracker staining, upregulated XBP1 and GRP78/BiP splicing. Remarkably, the systemic toxicity and blood compatibility profile of PEG@mTa2O5 can greatly improve successive therapeutic outcomes of NMs while reducing their adverse side effects. Overall, our findings suggested that PEG@mTa2O5-induced endothelium apoptosis was partially mediated by the activation of the endoplasmic reticulum stress-mitochondrial cascade.