Framework Nucleic Acids Enabled Pulmonary Artery Endothelial Cell Growth Inhibition by Targeting microRNA‐152

Abstract

Pulmonary artery vascular endothelial dysfunction plays a pivotal role in the occurrence and progression of pulmonary vascular remodeling (PVR). To address this, aberrantly expressed non‐coding microRNAs (miRNAs) are excellent therapeutic targets in human pulmonary artery endothelial cells (HPAECs). Here, we discovered and validated the overexpression of miRNA‐152 in HPAECs under hypoxia and its role in endothelial cell dysfunction. We constructed a framework nucleic acid nanostructure that harbors six protruding single‐stranded DNA segments that can fully hybridize with miRNA‐152 (DNT‐152). DNT‐152 was efficiently taken up by HPAECs with increasing time and concentration; it markedly induced apoptosis, and inhibited HPAEC growth under hypoxic conditions. Mechanistically, DNT‐152 silenced miRNA‐152 expression and upregulated its target gene Meox2, which subsequently inhibited the AKT/mTOR signaling pathway. These results indicate that miRNA‐152 in HPAECs may be an excellent therapeutic target against PVR, and that framework nucleic acids with carefully designed sequences are promising nanomedicines for noncancerous cells and diseases.

DNA nanoparticles targeting FOXO4 selectively eliminate cigarette smoke-induced senescent lung fibroblasts

“…The mode and parameters were set according to our previous research. 38 Cell uptake of DNA nanoparticles Senescent HFL-1 cells were seeded on glass bottom dishes or 6well dishes overnight. These cells were incubated with different concentrations of siFOXO4-NT-Cy5 in the presence of Lipofectame-3000 for indicated times.…”