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.