Targeting and promoting atherosclerosis regression using hybrid membrane coated nanomaterials via alleviated inflammation and enhanced autophagy

ABSTRACT Atherosclerosis is the leading cause of death and disability worldwide, which is lack of efficient strategy for targeted therapy. In this work, we reported a hybrid membrane coated graphene oxide quantum dots (GOQDs) nanomaterial loading atorvastatin (AT) to achieve targeted atherosclerosis therapy. In this biomimetic nanomaterial, macrophages membrane (Møm) was used to extend the half-life of AT and enhance the accumulation of AT in the atherosclerotic plaques. Meanwhile, red blood cell membrane (RBCm) was adopted to reduce the amount of Møm usage. Furthermore, hyaluronic acid (HA) was inserted into the hybrid membrane to enhance the internalization of nanomaterial into activated macrophages of atherosclerotic plaques. In vitro assay demonstrated that this nanomaterial can release AT in an acidic pH-responsive manner. In vivo assay demonstrated that both long-term low-dose and short-term high-dose regimens with favorable safety can effectively inhibit the development of the early atherosclerosis and markedly regress the progression of advanced atherosclerotic plaques, respectively. Molecular mechanism exploration indicated that the anti-atherosclerosis effect of the nanomaterial was mediated by alleviating inflammation to reduce lipid influx and enhancing autophagy to promote cholesterol efflux. Overall, this biomimetic nanomaterial provides an alternative for developing safe and efficient strategy for atherosclerosis therapy.