Overexpressed VLA-4 on endothelial cell membrane camouflaging the pathological reactive oxygen species responsive prodrug to enhance target therapy for atherosclerosis

Abstract

The development of atherosclerosis (AS) is closely related to inflammation. The common feature of inflammatory sites is upregulation of vascular cell adhesion molecule-1 (VCAM-1), which has a strong affinity with very late antigen-4 (VLA-4). Endothelial cell membranes overexpressing VLA-4 (OEM) were used to camouflage rapamycin nanoparticles (RAP NPs) with reactive oxygen species (ROS) responsiveness to construct biomimetic nanodrugs OEM@RAP NPs. These nanoparticles were capable of enhancing the active target drug delivery and ROS-responsive drug release under the pathological overexpression of VCAM-1 and accumulation of ROS stimulus. In vitro and in vivo investigations confirmed that OEM@RAP NPs could enhance the active target drug delivery to atherosclerotic plaques and increase drug accumulation in the focal site, thus improving the bioavailability of drugs, reducing side effects and inhibiting the occurrence and development of atherosclerosis.