Delivery of macromolecules into cytosol using liposomes containing hemolysin from Listeria monocytogenes
Delivery of macromolecules into cytosol using liposomes containing hemolysin from Listeria monocytogenes
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DOI：
10.1074/jbc.271.13.7249
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发表时间：
1996-03-29
影响因子：
4.8
通讯作者：
Swanson, JA
中科院分区：
文献类型：
--
作者：
Lee, KD;Oh, YK;Swanson, JA
细胞的胞液空间是治疗大分子输送的一个重要但相对难以触及的靶点。在这里，我们描述了大分子从含有李斯特菌溶血素O(LLO)的脂质体高效地输送到巨噬细胞的胞液空间，LLO是单核细胞增生性李斯特菌的溶血蛋白，通常介导细菌从吞噬小体进入胞浆。LLO被提纯并与其他将要输送的分子一起被pH敏感的脂质体包裹，当被骨髓来源的巨噬细胞内化时，这些脂质体迅速释放包裹的荧光染料，首先进入内囊，然后进入胞浆，而不会对细胞造成明显的损害。此外，根据主要组织相容性复合体(MHC)限制的卵清蛋白多肽的I类递呈来衡量，这些脂质体有效地将包裹的卵清蛋白运送到抗原处理和递呈的胞浆途径。因此，含LLO的脂质体为体内抗原或治疗分子的传递提供了一种有效的载体。
The cytosolic space of cells is an important but relatively inaccessible target for the delivery of therapeutic macromolecules. Here we describe the efficient delivery of macromolecules into the cytosolic space of macrophages from liposomes that contain listeriolysin O (LLO), the hemolytic protein of Listeria monocytogenes that normally mediates bacterial passage from phagosomes into cytosol, LLO was purified and encapsulated inside pH-sensitive liposomes, along with other molecules to be delivered, When internalized by bone marrow-derived macrophages, these liposomes rapidly released encapsulated fluorescent dye, first into endosomes and then into the cytosol, without measurably harming the cells. Furthermore, these liposomes efficiently delivered encapsulated ovalbumin to the cytosolic pathway of antigen processing and presentation, as measured by the major histocompatibility complex (MHC) class I-restricted presentation of peptides derived from ovalbumin. Delivery was significantly better than that obtained by other currently available liposome formulations, LLO-containing liposomes should therefore provide an efficient vehicle for delivery of antigens or therapeutic molecules in vivo.