Mesenchymal stem cell membrane-coated kaempferol biomimetic nanoformulation for the treatment of atherosclerosis

Atherosclerosis and its complications are highly prevalent worldwide, and managing oxidative stress in endothelial cells to alleviate abnormal inflammatory damage is a critical therapeutic approach. Nanomedicine delivery systems offer promising solutions by overcoming the limitations of surgical interventions and the off-target effects of oral drugs. In this study, we developed a modified mesenchymal stem cell membrane (MSCM)-encapsulated nanoparticle drug delivery system that effectively delivers kaempferol to atherosclerotic sites. These biomimetic nanoparticles were able to specifically target endothelial cells in an inflammatory environment while evading macrophage-mediated endocytosis. Moreover, the modified MSCM-encapsulated kaempferol nanoparticles (KPM) had a protective effect on oxidatively damaged endothelial cells. <i>In vivo</i>, the modified nanoparticles successfully migrated toward atherosclerotic lesions, as demonstrated in a mouse model of susceptible atherosclerotic plaques. Intravenous injection of KPM significantly reduced the lipid plaque load and improved plaque structure. Furthermore, the biosafety of KPM was comprehensively assessed both <i>in vitro</i> and <i>in vivo</i>, with no significant effects on blood count, lipid balance, cellular activity, body weight, or liver or kidney function. This is the first report of the use of MSCM to encapsulate kaempferol nanodrugs to treat atherosclerosis. This strategy presents a novel and effective therapeutic system for targeted delivery of antioxidant therapy to atherosclerotic sites, offering potential for the treatment of atherosclerosis in cardio-cerebrovascular diseases.