New methodology for liposome targeting to specific cells.
New methodology for liposome targeting to specific cells.
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脂质体靶向特定细胞的新方法。
DOI：
10.1111/j.1749-6632.1985.tb18412.x
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发表时间：
1985
影响因子：
5.2
通讯作者：
Matthay,K
中科院分区：
文献类型：
--
作者：
Papahadjopoulos,D;Heath,T;Bragman,K;Matthay,K
脂质体对不同细胞类型的特异性是通过与针对各种细胞表面抗原的单克隆抗体缀合来实现的。 L929 小鼠成纤维细胞被缀合有抗 H2Kk 的脂质体靶向。 K562 细胞是一种源自慢性粒细胞白血病的人类细胞系，是抗糖蛋白蛋白的靶标。抗 thy 1.1 靶向一种小鼠 T 淋巴瘤 AKR/J SL2；另一个，R1。 1、以抗H2Kk为目标。关于抗体导向脂质体作为药物递送系统的功效，建立了以下重要参数。(1)含有甲氨蝶呤-γ-天冬氨酸的靶向脂质体的细胞毒性比游离药物或非特异性脂质体高20-40倍。(2)使用甲氨蝶呤-γ-天冬氨酸等药物，这些药物在没有药物的情况下无法进入细胞。 载体，消除了可能从脂质体中泄漏的药物的非特异性效应。(3) 与抗体缀合的脂质体比可溶性抗体具有更高的化合价，并以高达 1000 倍的亲和常数与细胞结合。(4) 与细胞表面上一种以上配体相互作用的脂质体对可溶性配体对细胞缔合的抑制表现出明显的抵抗力。(5) 最佳脂质体大小似乎在 0.05 至 0.1 mu 之间变化，具体取决于靶细胞类型。
The specificity of liposomes for different cell types was achieved by conjugation to monoclonal antibodies directed against various cell surface antigens. L929 mouse fibroblast cells were targeted with liposomes conjugated to anti-H2Kk. K562 cells, a human line derived from chronic myelogenous leukemia, were targeted with antiglycophorin. One murine T-lymphoma, AKR/J SL2, was targeted with anti-thy 1.1; another, R1. 1, was targeted with anti-H2Kk. The following important parameters were established concerning efficacy of antibody-directed liposomes as a drug delivery system.(1) Targeted liposomes containing methotrexate-gamma-aspartate were 20-40 times more cytotoxic than the free drug or nonspecific liposomes.(2) The use of drugs such as methotrexate-gamma-aspartate, which are unable to enter cells without a carrier, eliminates the nonspecific effects of drug that may leak from the liposomes.(3) Liposomes conjugated to antibody have a higher valency than the soluble antibody and bind to cells with up to 1000-fold higher affinity constant.(4) Liposomes that interact with more than one type of ligand on the cell surface show marked resistance to inhibition of cell association by soluble ligands.(5) The optimal liposome size appears to vary from 0.05 to 0.1 mu, depending on target cell type.