Department of Biomedicine, Aarhus University, Ole Worms Alle 2, Aarhus, Denmark.
J Control Release. 2012 May 30;160(1):72-80. doi: 10.1016/j.jconrel.2012.01.034. Epub 2012 Jan 27.
The hemoglobin scavenger receptor CD163 is exclusively expressed in the monocytic lineage and preferentially in tissue resident macrophages of the M2 phenotype and in macrophages in sites of inflammation and tumor growth. In the present study we have designed liposomes specifically targeting CD163 by hydrophobic linkage of CD163-binding monoclonal antibodies to polyethylene glycol-coated liposomes ('stealth liposomes'). Targeting to the endocytic CD163 protein greatly increased the uptake of liposomes in CD163 transfected cells and macrophages as visualized by confocal microscopy and flow cytometry of cells exposed to CD163 targeting liposomes loaded with calcein. Strong cytotoxic effects were seen in CD163-expressing human monocytes by using the chemotherapeutic agent doxorubicin as cargo of the liposomes. In conclusion, the use of stealth liposomes modified to recognize CD163 is a potential way to target drugs to macrophages that support inflammatory and malignant processes.
清道夫受体 CD163 仅在单核细胞谱系中表达，并且在 M2 表型的组织驻留巨噬细胞和炎症及肿瘤生长部位的巨噬细胞中优先表达。在本研究中，我们通过将 CD163 结合单克隆抗体与聚乙二醇包被的脂质体疏水连接，设计了专门针对 CD163 的脂质体（“隐形脂质体”）。靶向内吞 CD163 蛋白极大地增加了脂质体在转染 CD163 的细胞和巨噬细胞中的摄取，这可以通过共聚焦显微镜和流式细胞术观察到，这些细胞暴露于负载钙黄绿素的靶向 CD163 的脂质体。当使用脂质体作为载药将化疗药物阿霉素递送至表达 CD163 的人单核细胞时，观察到强烈的细胞毒性作用。总之，使用修饰以识别 CD163 的隐形脂质体是将药物靶向支持炎症和恶性过程的巨噬细胞的一种潜在方法。
