Biomimetic nanoparticles: U937 cell membranes based core-shell nanosystems for targeted atherosclerosis therapy

Atherosclerosis (AS), with its intricate pathogenesis, is primarily responsible for the development and progression of cardiovascular diseases. Although drug development has made some achievements in AS therapy, limited targeting ability and rapid blood clearance remain great challenges for achieving superior clinical outcomes. Herein, ginsenoside (Re)- and catalase (CAT)-coloaded porous poly(lactic-coglycolic acid) (PLGA) nanoparticles (NPs) were prepared and then surface modified with U937 cell membranes (UCMs) to yield a dual targeted model and multimechanism treatment biomimetic nanosystem (Cat/Re@PLGA@UCM). The nanoparticles consisted of a core-shell spherical morphology with a favorable size of 112.7 ± 0.4 nm. Furthermore, UCM assisted the nanosystem in escaping macrophage phagocytosis and targeting atherosclerotic plaques. Meanwhile, loading with catalase might not only exhibit favorable antioxidant effects but also enable H₂O₂-responsive drug release ability. The Cat/Re@PLGA@UCM NPs also exhibited outstanding ROS scavenging properties, downregulating ICAM-1, TNF-α and IL-1β, while preventing angiogenesis to attenuate the progression of AS. Moreover, the nanodrugs displayed 2.7-fold greater efficiency in reducing the atherosclerotic area in ApoE^-/- mouse models compared to free Re. Our nanoformulation also displayed excellent biosafety in response to long-term administration. Overall, our study demonstrated the superiority of UCM-coated stimuli-responsive nanodrugs for effective and safe AS therapy.