Biomimetic Macrophages Inhibit Atherosclerosis in <i>ApoE</i>^<i>-</i><i>/</i>^<i>-</i> Mice through Inducing Macrophages Autophagy.

Abstract

Inflammation is an outstanding of countless deadly diseases such as atherosclerosis, triggered by chronic inflammation within the artery walls, which underlie a range of critical cardiovascular diseases. There is considerable evidence that defective autophagy and excessive production of reactive oxygen species are closely involved in the initiation and development of atherosclerosis. Reactive oxygen species-initiated autophagy dysfunction induces conspicuous cell apoptosis and causes the increase of foam macrophages. The treatment of atherosclerosis is majorly aimed at decreasing the cholesterol/lipid levels in blood at present and has no connection with regulating inflammation, the fundamental cause. Nevertheless, anti-inflammatory medicines are not clinically implemented in the therapy of atherosclerosis. M2 macrophages, aiding in the suppression of inflammation and clearance of cellular debris after apoptosis, play the important role of anti-inflammatory in atherosclerosis. A bionic M2 macrophages (M₂@Ir-TiO₂) are established to inhibit atherosclerosis through antioxidant and autophagy-inducing. In this work, Ir-TiO₂ not only quickly removes excess ROS but also induces autophagy in macrophages, reduces oxidized low-density lipoprotein intracellular, and finally inhibits foam cell formation. The advanced M₂@Ir-TiO₂ demonstrated good biocompatibility and effectively targeted and accumulated in atherosclerotic lesions. M₂@Ir-TiO₂ was shown to delay the progression of atherosclerosis significantly.