Machy P, Leserman L D
Biochim Biophys Acta. 1983 May 5;730(2):313-20. doi: 10.1016/0005-2736(83)90348-6.
We have compared drug transfer into target cells in vitro from liposomes of different sizes. Liposomes of mean diameter 800 A, 2000 A or 4000 A, containing the folate analogue, methotrexate, and the fluorophore, carboxyfluorescein, were covalently coupled to Staphylococcus aureus protein A. Cells of the murine k haplotype were preincubated with an anti-H-2Kk monoclonal antibody. Excess antibody was removed and then cells were incubated with liposomes. The number of cell-bound liposomes was determined by fluorimetry. The drug effect was assayed by the methotrexate-mediated inhibition of radiolabeled deoxyuridine uptake. The drug effect was more important in the case of the 800 A vesicles than for the larger liposomes, despite the fact that the quantity of drug bound to cells was several-fold greater for large liposomes than for small ones. Since fusion is excluded by the non-proportionality of drug binding and drug effect, the predominant manner of liposome entry seems to be endocytosis. At least for these in vitro studies, the endocytosis by target cells of small liposomes seems to be more efficient than that of large liposomes.
我们比较了不同大小脂质体在体外向靶细胞的药物转运情况。平均直径为800埃、2000埃或4000埃的脂质体，含有叶酸类似物甲氨蝶呤和荧光团羧基荧光素，它们与金黄色葡萄球菌蛋白A共价偶联。将小鼠k单倍型细胞与抗H-2Kk单克隆抗体预孵育。去除过量抗体后，再将细胞与脂质体孵育。通过荧光测定法确定细胞结合的脂质体数量。通过甲氨蝶呤介导的对放射性标记脱氧尿苷摄取的抑制作用来测定药物效果。尽管与细胞结合的药物量，大脂质体比小脂质体多几倍，但在800埃囊泡的情况下，药物效果比大脂质体更显著。由于药物结合与药物效果不成比例，排除了融合作用，脂质体进入细胞的主要方式似乎是内吞作用。至少对于这些体外研究而言，小脂质体被靶细胞内吞的效率似乎比大脂质体更高。
