Engineered extracellular vesicles demonstrate altered endocytosis and biodistribution and have superior oral siRNA delivery efficiency compared to lipid nanoparticles.

ABSTRACT: Oral administration of RNA therapeutics remains a major unsolved challenge due to currently insurmountable biological barriers. Extracellular vesicles (EVs) are natural carriers capable of traversing the intestinal barrier, but inefficient RNA loading into EVs in general severely limits the application of EVs for RNA delivery. Here, we utilize a microfluidic engineering platform to generate milk-derived EV-lipid nanoparticle (EV-LNP) hybrids for oral delivery of RNA. The process produced uniform nanoparticles (133 nm, polydispersity index 0.19) with >45 % dual-positive fusion efficiency, significantly outperforming freeze-thaw hybridization. Compared to conventional LNPs, EV-LNP hybrids exhibited lower cytotoxicity, altered epithelial uptake pathways, and markedly improved intestinal epith

SUBMITTER: Ding N 

PROVIDER: S-EPMC12621563 | biostudies-literature | 2025 Dec

REPOSITORIES: biostudies-literature