Tetrahedral framework nucleic acids‐based delivery of MicroRNA‐22 inhibits pathological neovascularization and vaso‐obliteration by regulating the Wnt pathway

Abstract The objective of this study was to investigate the effects and molecular mechanisms of tetrahedral framework nucleic acids‐microRNA22 (tFNAs‐miR22) on inhibiting pathological retinal neovascularization (RNV) and restoring physiological retinal vessels. A novel DNA nanocomplex (tFNAs‐miR22) was synthesised by modifying microRNA‐22 (miR22) through attachment onto tetrahedral frame nucleic acids (tFNAs), which possess diverse biological functions. Cell proliferation, wound healing, and tube formation were employed for in vitro assays to investigate the angiogenic function of cells. Oxygen‐induced retinopathy (OIR) model was utilised to examine the effects of reducing pathological neovascularization (RNV) and inhibiting vascular occlusion in vivo. In vitro, tFNAs‐miR22 demonstrated the ability to penetrate endothelial cells and effectively suppress cell proliferation, tube formation, and migration in a hypoxic environment. In vivo, tFNAs‐miR22 exhibited promising results in reducing RNV and promoting the restoration of normal retinal blood vessels in OIR model through modulation of the Wnt pathway. This study provided a theoretical basis for the further understanding of RNV, and highlighted the innovative and potential of tFNAs‐miR22 as a therapeutic option for ischemic retinal diseases.