Brain-targeting gene delivery using a rabies virus glycoprotein peptide modulated hollow liposome: bio-behavioral study

In this study, a novel hollow liposome modified with a rabies virus glycoprotein peptide (RVG-liposome) was designed and synthesized for siRNA delivery to the brain. The resultant RVG-liposome was about 91 nm in diameter with a regular globular shape and hollow structure. siRNA was successfully encapsulated into the hollow cores of the RVG-liposome, achieving ∼75% entrapment efficacy while maintaining the nanodimensions of the RVG-liposome. The siRNA-loaded RVG-liposome can be effectively internalized and subsequently releases siRNA in bone marrow macrophages. With siRNA loading, the RVG-liposome mediated effective siRNA delivery and resulted in high transfection efficiency in U87 cells. MTT assay demonstrated that neither the RVG-liposomes themselves nor siRNA-loaded RVG-liposome showed cytotoxicity, even at high concentrations. Moreover, in vivo live imaging and fresh frozen sections showed that the RVG-liposome has the ability to cross the blood–brain barrier (BBB) and was preferably accumulated in the brain. Such a hollow RVG-liposome holds great promise as a non-viral vector for efficient and brain-targeting gene delivery.