Objectives: The purpose of this study was to investigate the treatment effect and molecular mechanism of tetrahedral framework nucleic acids (tFNAs), novel self-assembled nucleic acid nanomaterials, in diffuse BMEC injury after SAH.
Materials and methods: tFNAs were synthesized from four ssDNAs. The effects of tFNAs on SAH-induced diffuse BMEC injury were explored by a cytotoxicity model induced by hemin, a breakdown product of hemoglobin, in vitro and a mouse model of SAH via internal carotid artery puncture in vivo. Cell viability assays, wound healing assays, transwell assays, and tube formation assays were performed to explore cellular function like angiogenesis.
Results: In vitro cellular function assays demonstrated that tFNAs could alleviate hemin-induced injury, promote angiogenesis, and inhibit apoptosis in hemin cytotoxicity model. In vivo study using H&E and TEM results jointly indicated that the tFNAs attenuate the damage caused by SAH in situ, showing restored number of BMECs in the endothelium layer and more tight intercellular connectivity. Histological examination of SAH model animals confirmed the results of the in vitro study, as tFNAs exhibited treatment effects against diffuse BMEC injury in the cerebral microvascular bed.
Conclusions: Our study suggests the potential of tFNAs in ameliorating diffuse injury to BMECs after SAH, which laid theoretical foundation for the further study and use of these nucleic acid nanomaterials for tissue engineering vascularization.
Keywords: PI3K-AKT-mTOR signaling pathways; anti-apoptosis; diffuse brain microvascular endothelial cells injury; subarachnoid hemorrhage; tetrahedral DNA nanostructures.
© 2022 The Authors. Cell Proliferation published by John Wiley & Sons Ltd.