Antigen delivery to macrophages using liposomal nanoparticles targeting sialoadhesin/CD169.

Antigen delivery to macrophages using liposomal nanoparticles targeting sialoadhesin/CD169.
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DOI:
10.1371/journal.pone.0039039
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发表时间:
2012
期刊:
影响因子:
3.7
通讯作者:
Paulson JC
Paulson JC
中科院分区:
综合性期刊3区
文献类型:
--
作者:
Chen WC;Kawasaki N;Nycholat CM;Han S;Pilotte J;Crocker PR;Paulson JC

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唾液酸粘附素(Sn,Siglec-1,CD 169)是巨噬细胞上表达的唾液酸结合Ig样凝集素(siglec)家族的成员。其巨噬细胞特异性表达使其成为通过Sn介导的内吞作用将抗原递送至组织巨噬细胞的有吸引力的靶标。在这里,我们描述了一种新的方法,用于提供抗原的巨噬细胞使用脂质体纳米粒子显示高亲和力聚糖配体的锡。靶向Sn的脂质体选择性地结合到表达Sn的细胞并被其内化,并且随着时间的推移在细胞内积累。我们的研究结果表明,配体修饰的脂质体对Sn具有特异性,因为它们被来自野生型而不是Sn−/−小鼠的骨髓源性巨噬细胞摄取。重要的是,Sn靶向脂质体显著增强了抗原向巨噬细胞的递送,以呈递给抗原特异性T细胞并使其增殖。总之,这些数据提供了对使用Sn配体修饰的脂质体纳米颗粒将抗原细胞特异性靶向和递送至巨噬细胞的细胞内细胞器的潜力的见解。
Sialoadhesin (Sn, Siglec-1, CD169) is a member of the sialic acid binding Ig-like lectin (siglec) family expressed on macrophages. Its macrophage specific expression makes it an attractive target for delivering antigens to tissue macrophages via Sn-mediated endocytosis. Here we describe a novel approach for delivering antigens to macrophages using liposomal nanoparticles displaying high affinity glycan ligands of Sn. The Sn-targeted liposomes selectively bind to and are internalized by Sn-expressing cells, and accumulate intracellularly over time. Our results show that ligand decorated liposomes are specific for Sn, since they are taken up by bone marrow derived macrophages that are derived from wild type but not Sn−/− mice. Importantly, the Sn-targeted liposomes dramatically enhance the delivery of antigens to macrophages for presentation to and proliferation of antigen-specific T cells. Together, these data provide insights into the potential of cell-specific targeting and delivery of antigens to intracellular organelles of macrophages using Sn-ligand decorated liposomal nanoparticles.
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