Salord J, Schuber F
Laboratoire de Chimie Enzymatique (CNRS UA 1182), Université Louis Pasteur, Strasbourg, France.
Biochim Biophys Acta. 1988 Sep 16;971(2):197-206. doi: 10.1016/0167-4889(88)90192-9.
We have studied the growth-inhibitory potency of methotrexate and methotrexate-gamma-aspartate encapsulated in liposomes conjugated to ligands of ecto-NAD+-glycohydrolase (Salord, J. et al., Biochim. Biophys. Acta 886 (1986) 64-75). The ability of targeted liposomes to enhance growth inhibition, which amounted to a 4-fold reduction of the drug concentration required to inhibit cell growth by 50% as compared to nontargeted liposomes, was observed only with cells expressing this ecto-enzyme activity, i.e., Swiss 3T3 fibroblasts and RAJI, a Burkitt-type lymphoma cell line. Delivery of the encapsulated drugs was inhibited by NH4Cl and varied with the endocytic capacity of the cells. Only small unilamellar vesicles affected the growth of the lymphoma cells, whereas the fibroblasts were more sensitive to large unilamellar vesicles. With vesicles of appropriate size, there was a good correlation between the specific binding of the targeted liposomes to cells and drug delivery. Our results suggest that ecto-NAD+-glycohydrolase can provide a recognition site on target cells and mediate the internalization of targeted liposomes by a mechanism most probably related to adsorptive endocytosis.
我们研究了包裹在与胞外NAD⁺-糖水解酶配体偶联的脂质体中的甲氨蝶呤和甲氨蝶呤-γ-天冬氨酸的生长抑制效力（Salord，J.等人，《生物化学与生物物理学学报》886（1986）64-75）。仅在表达这种胞外酶活性的细胞，即瑞士3T3成纤维细胞和伯基特型淋巴瘤细胞系RAJI中，观察到靶向脂质体增强生长抑制的能力，与非靶向脂质体相比，这使得抑制细胞生长50%所需的药物浓度降低了4倍。包裹药物的递送受到氯化铵的抑制，并且随细胞的内吞能力而变化。只有小单层囊泡影响淋巴瘤细胞的生长，而成纤维细胞对大单层囊泡更敏感。对于合适大小的囊泡，靶向脂质体与细胞的特异性结合和药物递送之间存在良好的相关性。我们的结果表明，胞外NAD⁺-糖水解酶可以在靶细胞上提供一个识别位点，并通过一种很可能与吸附性胞吞作用相关的机制介导靶向脂质体的内化。
