Framework Nucleic Acids Loaded with Quercetin: Protecting Retinal Neurovascular Unit Via the Protein Kinase B/Heme Oxygenase-1 Pathway

Retinal neovascular disease is a leading cause of vision loss and blindness globally. It occurs when abnormal new blood vessels form in the retina. In this study, we utilized tetrahedral framework nucleic acids (tFNAs) as vehicles to load quercetin (QUE), a small-molecule flavonoid, forming a deoxyribonucleic acid (DNA) nanocomplex, tFNAs-QUE. Our data show this nanocomplex inhibits pathological neovascularization, reduces the area of retinal nonperfusion area, protects retinal neurons, and preserves the visual function. Further, we discovered that tFNAs-QUE selectively upregulates the AKT/Nrf2/HO-1 signaling pathway, which can suppress pathological vascular growth and exert antioxidative effects. Therefore, this study presents a promising small-molecule-loading mechanism for the treatment of ischemic retinal diseases.