A cell membrane-hybridized nanocarrier-based RNA delivery system for ocular neovascular diseases

Abstract

Ocular neovascularization is a common pathological feature of various blinding eye diseases. Current anti vascular endothelial growth factor (VEGF) therapies face challenges such as low response rates, frequent injections, and multiple complications. RNA-based therapeutics offer advantages including strong targeting capability and reversible modulation, but encounter obstacles like low delivery efficiency, susceptibility to degradation, and lack of targeting specificity. This study developed an endothelial cell membrane-hybridized lipid nanoparticle that achieve specific targeting of neovascular endothelial cells through "homing effects". The carrier exhibits excellent biocompatibility, high small interfering RNA (siRNA) delivery efficiency, and lysosomal escape capability, effectively penetrating the vitreous barrier. In a laser-induced choroidal neovascularization mouse model, it significantly enhanced drug accumulation at the lesion site, providing a safe and effective delivery strategy for RNA therapy of ocular neovascular diseases.