Targeted Delivery of Anti‐miR‐712 by VCAM1‐Binding Au Nanospheres for Atherosclerosis Therapy

Abstract Atherosclerosis is a chronic, inflammatory disease of the vascular wall, which preferentially develops in regions under disturbed flow ( d‐flow ). Once inflamed, the endothelial cells initiate a signaling cascade that culminates in the expression of pro‐atherogenic genes such as mRNAs and miRNAs. Here we demonstrate that vascular cell adhesion molecule 1 (VCAM1), which is highly expressed on the surface of endothelial cells under d‐flow, can serve as a marker for the targeted delivery of drug to the inflamed endothelium. We could selectively deliver anti‐miR‐712, an inhibitor of a key pro‐atherogenic miRNA, to VCAM1‐expressing immortalized mouse aortic endothelial cells (iMAECs) by hybridizing the inhibitor with a carrier DNA that has a complementary sequence and is conjugated to the surface of Au nanospheres. Our results suggest that the combination of VCAM1‐binding peptide and Au nanosphere could provide an effective strategy for the selective delivery of anti‐athero‐miRNAs or other drugs into inflamed endothelium for the purpose of inhibiting the formation of atherosclerotic plaques.