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半乳糖修饰脂质体作为一种有效的鼻腔免疫给药靶向抗原提呈细胞载体的应用。

Application of galactose-modified liposomes as a potent antigen presenting cell targeted carrier for intranasal immunization.

机构信息

School of Pharmacy, College of Medicine, National Taiwan University, Taipei, Taiwan.

出版信息

Acta Biomater. 2013 Mar;9(3):5681-8. doi: 10.1016/j.actbio.2012.11.007. Epub 2012 Nov 14.

Abstract

The mucosal immune system produces secretory IgA (sIgA) as the first line of defense against invasion by foreign pathogens. Our aim was to develop a galactose-modified liposome as a targeted carrier which can be specifically recognized by macrophage, one of the most important antigen presenting cells. First, galactose was covalently conjugated with 1,2-didodecanoyl-sn-glycero-3-phosphoethanolamine (DLPE) to give a targeted ligand, a galactosyl lipid. The galactosyl lipid was then incorporated into a liposomal bilayer to form a galactosylated liposome carrier. Further, the ovalbumin (OVA) was encapsulated into the galactosylated liposome carriers and mice were intranasally immunized. Confocal laser scanning microscopy and flow cytometry analysis showed that the targeted galactosylated liposome carrier had a higher uptake rate than unmodified liposomes. The targeted galactosylated liposome induced higher levels of tumor necrosis factor-α and interleukin-6 production than unmodified liposomes (P<0.05). Furthermore, 6-week-old BALB/c female mice immunized with the OVA-encapsulated targeted galactosylated liposome had significantly higher OVA-specific s-IgA levels in the nasal and lung wash fluid (P<0.05). In addition, the targeted galactosylated liposome simultaneously augmented the serum IgG antibody response. In summary, the OVA-encapsulated targeted galactosylated liposome induced significantly higher mucosal IgA and systemic IgG antibody titers and is a potential antigen delivery carrier for further clinical applications.

摘要

黏膜免疫系统产生分泌型免疫球蛋白 A(sIgA)作为抵御外来病原体入侵的第一道防线。我们的目的是开发一种半乳糖修饰的脂质体作为靶向载体,该载体可以被巨噬细胞(一种最重要的抗原提呈细胞)特异性识别。首先,半乳糖通过共价键与 1,2-二肉豆蔻酰-sn-甘油-3-磷酸乙醇胺(DLPE)结合,得到靶向配体半乳糖脂质。然后,将半乳糖脂质掺入脂质体双层中以形成半乳糖化脂质体载体。进一步将卵清蛋白(OVA)包封入半乳糖化脂质体载体中,并通过鼻腔免疫小鼠。共聚焦激光扫描显微镜和流式细胞术分析表明,靶向半乳糖化脂质体载体的摄取率高于未修饰的脂质体。与未修饰的脂质体相比,靶向半乳糖化脂质体诱导产生更高水平的肿瘤坏死因子-α和白细胞介素-6(P<0.05)。此外,用包封的 OVA 的靶向半乳糖化脂质体免疫 6 周龄 BALB/c 雌性小鼠后,鼻腔和肺灌洗液中的 OVA 特异性 s-IgA 水平显著升高(P<0.05)。此外,靶向半乳糖化脂质体同时增强了血清 IgG 抗体反应。综上所述,OVA 包封的靶向半乳糖化脂质体可诱导黏膜 IgA 和系统 IgG 抗体滴度显著升高,是一种有潜力的抗原递送载体,可用于进一步的临床应用。

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