Cell membrane-based nanovesicles as potential drug delivery systems for atherosclerosis therapy

Atherosclerosis is the main underlying cause of death, being originated by endothelial dysfunction, which favor the recruitment of different cell types and expression of several factors contributing to plaque development and growth. Current standard treatments are focused on the systemic administration of statins, which reduce the blood cholesterol levels and provide additional anti-inflammatory and plaque-stabilizing effects but also present important adverse side effects such as myopathy and liver damage, among others. To overcome such drawbacks, drug delivery systems have emerged to directly target the diseased vessel tissue, control drug release, and subsequently enhance the therapeutic outcome. In this regard, biomimetic nanovesicles (NVs) derived from cell membranes, exhibit superior biocompatibility, evade immune system recognition and have natural targeting capabilities, making them promising candidates as advanced drug nanocarriers. In this study, we present the development, characterization and therapeutic activity of pravastatin-loaded nanovesicles (PRA-loaded NVs) derived from RAW 264.7 macrophage cell membranes. The obtained PRA-loaded NVs maintained the structure and activity of integrin receptors as CD49d and CD11b which interact with overexpressed VCAM and ICAM-I receptors in inflamed vascular endothelial tissue and thus favoring potential targeting. In addition, NVs showed suitable encapsulation and sustained PRAV release, high biocompatibility, and efficient cellular uptake. Functional assays also confirmed the preservation of PRA therapeutic effect by reducing pro-inflammatory cytokines and promoting cholesterol release from foam cells. Hence, these findings highlight the potential of biomimetic NVs as innovative therapeutic agents for atherosclerosis treatment.