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Grapefruit-derived Nanovectors Delivering Therapeutic miR17 Through an Intranasal Route Inhibit Brain Tumor Progression.

Xiaoying Zhuang,Y. Teng,Abhilash Samykutty,J. Mu,Zhong‐bin Deng,Lifeng Zhang,Pengxiao Cao,Y. Rong,Jun Yan,Donald R. Miller,Huang‐Ge Zhang

Published 2016 in Molecular Therapy

ABSTRACT

The lack of access to the brain is a major obstacle for central nervous system drug development. In this study, we demonstrate the capability of a grapefruit-derived nanovector (GNV) to carry miR17 for therapeutic treatment of mouse brain tumor. We show that GNVs coated with folic acid (FA-GNVs) are enhanced for targeting the GNVs to a folate receptor-positive GL-26 brain tumor. Additionally, FA-GNV-coated polyethylenimine (FA-pGNVs) not only enhance the capacity to carry RNA, but the toxicity of the polyethylenimine is eliminated by the GNVs. Intranasal administration of miR17 carried by FA-pGNVs led to rapid delivery of miR17 to the brain that was selectively taken up by GL-26 tumor cells. Mice treated intranasally with FA-pGNV/miR17 had delayed brain tumor growth. Our results demonstrate that this strategy may provide a noninvasive therapeutic approach for treating brain-related disease through intranasal delivery.

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