ROS-scavenging anti-inflammatory nucleic acid delivery system for targeted treatment of atherosclerosis

Abstract

Atherosclerosis (AS) is a pathological condition predisposing to most major cardiovascular diseases and requiring prompt diagnosis and treatment. Inflammation is a central factor in the progression of AS, which is exacerbated by elevated reactive oxygen species (ROS) levels at the site of the lesion. The modulation of inflammation on its own is ineffective at controlling the progression of AS because of the influence of ROS. Therefore, this study aimed to introduce the ROS scavenger 2,2,6,6-tetramethylpiperidinooxy (Tem) and the targeted peptide VHPK in combination with an anti-inflammatory interleukin (IL)− 10 plasmid (pIL-10) to construct a cationic nucleic acid delivery system (PGED-Tem-2-V/pIL-10) for treating AS. PGED-Tem-2-V/pIL-10 targeted atherosclerotic lesions by binding to vascular cell adhesion molecule-1 (VCAM-1), thereby improving therapeutic efficiency and reducing the needed dosing frequency. In terms of therapeutic efficacy, PGED-Tem-2-V/pIL-10 effectively reduced the overproduction of ROS, decreased the expression of pro-inflammatory cytokines, and inhibited apoptosis, thus breaking the vicious cycle of inflammation and alleviating the progression of AS. PGED-Tem-2-V also has performance of magnetic resonance imaging, allowing for diagnosing AS-related conditions. PGED-Tem-2-V/pIL-10 had an excellent biosafety profile, displaying the potential to be an effective therapeutic system for treating other oxidative stresses and inflammatory diseases besides AS.