Liposomes are potential drug carriers for atherosclerosis therapy due to low immunogenicity and ease of surface modifications that allow them to have prolonged circulation half-life and specifically target atherosclerotic sites to increase uptake efficiency. However, the effects of their size, charge, and lipid compositions on macrophage and foam cell behaviour are not fully understood. In this study, liposomes of different sizes (60 nm, 100 nm and 180 nm), charges (−40 mV, −20 mV, neutral, +15 mV and +30 mV) and lipid compositions (1,2-dipalmitoyl-sn-glycero-3-phosphatidylcholine, 1,2-dipalmitoyl-sn-glycero-3-phosphocholine, L-a-phosphatidylcholine, and egg sphingomyelin) were synthesized, characterized and exposed to macrophages and foam cells. Compared to 100 nm neutral 1,2-dipalmitoyl-sn-glycero-3-phosphatidylcholine (DPPC) liposomes, flow cytometry and confocal imaging indicated that cationic liposomes and 1,2-dipalmitoyl-sn-glycero-3-phosphocholine (DSPC) liposomes were internalized more by both macrophages and foam cells. Through endocytosis inhibition, phagocytosis and clathrin-mediated endocytosis were identified as the dominant mechanisms of uptake. Anionic and DSPC liposomes induced more cholesterol efflux capacity in foam cells. These results provide a guide for the optimal size, charge, and lipid composition of liposomes as drug carriers for atherosclerosis treatment.

脂质体是用于动脉粥样硬化治疗的潜在药物载体，因为其免疫原性低且易于表面修饰，使其具有延长的循环半衰期并专门针对动脉粥样硬化部位以提高摄取效率。然而，它们的大小、电荷和脂质成分对巨噬细胞和泡沫细胞行为的影响尚不完全清楚。在这项研究中，不同大小（60 nm、100 nm 和 180 nm）、电荷（-40 mV、-20 mV、中性、+15 mV 和 +30 mV）和脂质组合物（1,2-二棕榈酰-sn -甘油-3-磷脂酰胆碱、1,2-二棕榈酰-sn-甘油-3-磷酸胆碱、La-磷脂酰胆碱和卵鞘磷脂) 被合成、表征并暴露于巨噬细胞和泡沫细胞。与 100 nm 中性 1,2-二棕榈酰-sn-甘油-3-磷脂酰胆碱 (DPPC) 脂质体相比，流式细胞术和共聚焦成像表明阳离子脂质体和 1,2-二棕榈酰-sn-甘油-3-磷酸胆碱 (DSPC) 脂质体更多地被巨噬细胞和泡沫细胞内化。通过内吞作用抑制，吞噬作用和网格蛋白介导的内吞作用被确定为摄取的主要机制。阴离子和 DSPC 脂质体在泡沫细胞中诱导更多的胆固醇流出能力。这些结果为脂质体作为动脉粥样硬化治疗药物载体的最佳尺寸、电荷和脂质组成提供了指导。吞噬作用和网格蛋白介导的内吞作用被确定为摄取的主要机制。阴离子和 DSPC 脂质体在泡沫细胞中诱导更多的胆固醇流出能力。这些结果为脂质体作为动脉粥样硬化治疗药物载体的最佳尺寸、电荷和脂质组成提供了指导。吞噬作用和网格蛋白介导的内吞作用被确定为摄取的主要机制。阴离子和 DSPC 脂质体在泡沫细胞中诱导更多的胆固醇流出能力。这些结果为脂质体作为动脉粥样硬化治疗药物载体的最佳尺寸、电荷和脂质组成提供了指导。