Department of Chemical Physiology, The Scripps Research Institute, La Jolla, California, USA.
PLoS One. 2012;7(6):e39039. doi: 10.1371/journal.pone.0039039. Epub 2012 Jun 19.
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.
唾液酸结合免疫球蛋白样凝集素 1（Sn、Siglec-1、CD169）是表达于巨噬细胞的唾液酸结合免疫球蛋白样凝集素（siglec）家族成员。因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，我们描述了一种使用展示 Sn 高亲和力糖配体的脂质体纳米颗粒将抗原递送至巨噬细胞的新方法。Sn 靶向脂质体选择性地与表达 Sn 的细胞结合并被其内化，并且随着时间的推移在细胞内积累。我们的结果表明，配体修饰的脂质体是特异性针对 Sn 的，因为它们被源自野生型但不是 Sn(-/-) 小鼠的骨髓来源的巨噬细胞摄取。重要的是，Sn 靶向脂质体显著增强了抗原向巨噬细胞的递呈，从而促进抗原特异性 T 细胞的增殖。总之，这些数据提供了使用 Sn 配体修饰的脂质体纳米颗粒将抗原靶向和递送至巨噬细胞的细胞内细胞器的潜在见解。
