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

TL;DR

This study shows that a DNA nanocomplex delivering microRNA-22 can reduce harmful blood vessel growth in the retina by regulating the Wnt pathway.

Contribution

A novel DNA nanocomplex (tFNAs-miR22) is developed for targeted delivery of miR22 to inhibit retinal neovascularization.

Findings

tFNAs-miR22 suppressed cell proliferation and migration in a hypoxic environment in vitro.

In vivo, tFNAs-miR22 reduced pathological retinal neovascularization and restored normal blood vessels.

The therapeutic effect was achieved through modulation of the Wnt signaling 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.

We selected tetrahedral framework nucleic acids (tFNAs) as a vector for microRNA22‐3p (miR22) to synthesise a tetrahedral framework nucleic acids‐microRNA22 (tFNAs‐miR22) complex. We investigated the regulation of tFNAs‐miR22 on blood vessels in vivo and in vitro via Wnt pathway, as a therapeutic option for ischemic retinal diseases.

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