Suppression of Retinal Neovascularisation by Tetrahedral Framework Nucleic Acids‐Resveratrol Via Dual Anti‐Angiogenesis and Anti‐Inflammation

Retinal neovascular diseases, such as retinopathy of prematurity and diabetic retinopathy, threaten vision by disrupting retinal structure and function through pathological neovascularisation and chronic inflammation. Existing anti-VEGF therapies primarily target angiogenesis, offering limited control over inflammation and requiring repeated administration. Here, we developed a resveratrol (RSV)-loaded tetrahedral framework nucleic acid nanostructure (tFNAs-RSV) to achieve concurrent anti-angiogenic and anti-inflammatory effects. tFNAs provided a biocompatible, stable and penetration-efficient carrier that enhanced RSV ocular delivery and bioactivity. In hypoxia-induced retinal neovascularisation models, tFNAs-RSV markedly reduced neovascular lesion area, vascular leakage and retinal inflammatory cell infiltration. Mechanistically, tFNAs-RSV suppressed HIF-1 signalling and inhibited the p38 MAPK pathway and NF-κB p65 pathway. Collectively, these results validate tFNAs-RSV as a promising nanoplatform for treating retinal neovascular diseases, with an emphasis on inhibiting neovascularisation and inflammation.