Abstract
Atherosclerosis (AS) is a prevalent chronic vascular inflammatory disease globally, initiated by injury to vascular endothelial cells (VECs). Macrophages play a pivotal role in disease pathogenesis, involving lipid metabolism and inflammation. The application of nanomaterials has been hindered by their rapid clearance by the immune system. Utilizing macrophage cell membranes can mitigate abnormal immune responses and induce a "homing" effect. Here, M2 macrophage cell membranes (M2) were coated onto berberine polylactic-hydroxylase-polylactide (PLGA) nanoparticles (BBR NPs), employing M2 macrophage immune escape, "homing" ability, and membrane coating nanotechnology, and loaded with mannose (Man) to create bionic nanoparticles (BBR NPs@Man/M2). Subsequently, the physical properties of BBR NPs@Man/M2 were characterized. The biocompatibility and biological function of BBR NPs@Man/M2 were assessed in vitro. Finally, the targeting, therapeutic efficacy, and safety of BBR NPs@M2 were investigated in an AS mouse model. The newly developed BBR NPs@Man/M2 exhibited good biocompatibility. Owing to their M2 coating, the nanoparticles effectively targeted macrophages in vitro, inducing a shift from a pro-inflammatory to an anti-inflammatory state. This transition reduced inflammation in endothelial cells and facilitated the repair of damaged endothelial cells. Moreover, M2-coated nanoparticles efficiently targeted and accumulated in atherosclerotic lesions in vivo. Following four weeks of treatment, BBR NPs@Man/M2 significantly delayed AS progression. Furthermore, BBR NPs@Man/M2 demonstrated a good safety profile after long-term administration. In conclusion, BBR NPs@Man/M2 effectively and safely inhibited AS progression. Biomimetic nanoparticles represent a promising approach for the safe and effective delivery of anti-AS drugs.