Nanocarriers such as liposomes have been attracting attention as novel therapeutic methods for inflammatory autoimmune diseases such as rheumatoid arthritis and ulcerative colitis. The physicochemical properties of intravenously administered nanomedicines enable them to target inflamed tissues passively. However, few studies have attempted to determine the influences of nanoparticle surface characteristics on inflammation site accumulation. Here, we aimed to study the effects of polyethylene glycol (PEG) modification and surface charge on liposome ability to accumulate in inflammatory sites and be uptake by macrophages. Four different liposome samples with different PEG modification and surface charge were prepared. Liposome accumulation in the inflammation sites of arthritis and ulcerative colitis model mice was evaluated by using in vivo imaging. There was greater PEG-modified than unmodified liposome accumulation at all inflammation sites. There was greater anionic than cationic liposome accumulation at all inflammation sites. The order in which inflammation site accumulation was confirmed was PEG-anionic > PEG-cationic > anionic > cationic. PEG-anionic liposomes had ~2.5× higher fluorescence intensity than PEG-cationic liposomes, and the PEG-liposomes had ~2× higher fluorescence intensity than non-PEG liposomes. All liposomes have not accumulated at the inflammation sites in healthy mice. Furthermore, cationic liposomes were taken up to ~10× greater extent by RAW264.7 murine macrophages. Thus, PEG-cationic liposomes that have the ability to accumulate in inflammatory sites via intravenous administration and to be taken up by macrophages could be useful.

中文翻译：

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通过静脉注射对脂质体被动炎症部位积聚进行体内荧光成像，重点关注其表面电荷和 PEG 修饰

脂质体等纳米载体作为类风湿性关节炎和溃疡性结肠炎等炎症性自身免疫性疾病的新型治疗方法而受到关注。静脉注射纳米药物的理化特性使其能够被动地靶向发炎组织。然而，很少有研究试图确定纳米颗粒表面特性对炎症部位积累的影响。在这里，我们的目的是研究聚乙二醇（PEG）修饰和表面电荷对脂质体在炎症部位积聚和被巨噬细胞摄取的能力的影响。制备了四种具有不同PEG修饰和表面电荷的不同脂质体样品。通过体内成像评估关节炎和溃疡性结肠炎模型小鼠炎症部位的脂质体积累。在所有炎症部位，PEG 修饰的脂质体积累量均高于未修饰的脂质体。所有炎症部位的阴离子脂质体积累量均大于阳离子脂质体积累量。确认炎症部位蓄积的顺序为PEG-阴离子>PEG-阳离子>阴离子>阳离子。PEG-阴离子脂质体的荧光强度比PEG-阳离子脂质体高约2.5倍，PEG-脂质体的荧光强度比非PEG脂质体高约2倍。所有脂质体均未在健康小鼠的炎症部位积聚。此外，RAW264.7 鼠巨噬细胞对阳离子脂质体的吸收程度提高了约 10 倍。因此，能够通过静脉内给药在炎症部位积聚并被巨噬细胞吸收的PEG-阳离子脂质体可能是有用的。