Issue 2, 2023

Attenuating endothelial leakiness with self-assembled DNA nanostructures for pulmonary arterial hypertension

Abstract

Vascular endothelium dysfunction plays an important role in oncological and pulmonary diseases. Endothelial barrier dysfunction is the initial step of pulmonary vascular remodeling (PVR) and pulmonary arterial hypertension. Upregulation of a pro-autophagy protein Atg101 in the endothelial cells triggered a cascade of intracellular events that leads to endothelial dysfunction through apoptosis. Herein, we proposed a strategy that used endothelial targeting DNA nanostructures to deliver Atg101 siRNA (siAtg101) as a safe, biocompatible “band-aid” to restore pulmonary arterial endothelial barrier integrity within the intricate milieu of pulmonary cells and the pulmonary vasculature. The siAtg101 and aptamer conjugated DNA nanostructures were found to attenuate hypoxia-induced pulmonary endothelial leakiness with surprisingly high selectivity and efficacy. Further in vivo study revealed that functionalized DNA nanostructures likewise attenuated the vascular remodeling in a monocrotaline-induced PVR mouse model. Mechanistically, functionalized DNA nanostructures suppressed PVR by knocking down Atg101, which in turn, downregulated Beclin-1 and subsequently upregulated VE-cadherin to restore endothelial cells’ adherin junctions. This work opened a new window for future nanomaterial design that directly addresses the interfacial endothelial cell layer that often stands between the blood and many diseased sites of nanotherapeutic interest.

Graphical abstract: Attenuating endothelial leakiness with self-assembled DNA nanostructures for pulmonary arterial hypertension

Supplementary files

Article information

Article type
Communication
Submitted
26 Jūl. 2022
Accepted
09 Dec. 2022
First published
15 Dec. 2022

Nanoscale Horiz., 2023,8, 270-278

Attenuating endothelial leakiness with self-assembled DNA nanostructures for pulmonary arterial hypertension

Q. Liu, D. Wu, B. He, X. Ding, Y. Xu, Y. Wang, M. Zhang, H. Qian, D. T. Leong and G. Wang, Nanoscale Horiz., 2023, 8, 270 DOI: 10.1039/D2NH00348A

To request permission to reproduce material from this article, please go to the Copyright Clearance Center request page.

If you are an author contributing to an RSC publication, you do not need to request permission provided correct acknowledgement is given.

If you are the author of this article, you do not need to request permission to reproduce figures and diagrams provided correct acknowledgement is given. If you want to reproduce the whole article in a third-party publication (excluding your thesis/dissertation for which permission is not required) please go to the Copyright Clearance Center request page.

Read more about how to correctly acknowledge RSC content.

Social activity

Spotlight

Advertisements