SELECTIVE DELIVERY OF DRUGS TO MACROPHAGES THROUGH A HIGHLY SPECIFIC RECEPTOR - AN EFFICIENT CHEMOTHERAPEUTIC APPROACH AGAINST LEISHMANIASIS
SELECTIVE DELIVERY OF DRUGS TO MACROPHAGES THROUGH A HIGHLY SPECIFIC RECEPTOR - AN EFFICIENT CHEMOTHERAPEUTIC APPROACH AGAINST LEISHMANIASIS
复制标题
DOI：
10.1016/0006-2952(89)90007-5
复制
发表时间：
1989-09-15
影响因子：
5.8
通讯作者：
BASU, SK
中科院分区：
文献类型：
--
作者：
CHAUDHURI, G;MUKHOPADHYAY, A;BASU, SK
甲氨蝶呤（Mtx）与马来酰化牛血清白蛋白（Mtx-MBSA）的结合物通过乙酰化低密度脂蛋白的多阴离子结合位点被培养的仓鼠腹腔巨噬细胞摄取和降解。Mtx-MBSA还消除培养的仓鼠腹腔巨噬细胞中杜氏利什曼原虫的细胞内无鞭毛体，比游离Mtx有效约3倍。Mtx-MBSA对寄生的巨噬细胞的抗利什曼原虫作用被MBSA、溶酶体抑制剂（氯喹和莫能菌素）和Mtx的代谢拮抗剂（叶酸和亚叶酸）阻断。注射的125 I标记的Mtx-MBSA的放射性积聚的主要部位是富含巨噬细胞的组织，即肝脏和脾脏。这些结果表明，Mtx-MBSA将确保快速和有效地杀死由巨噬细胞窝藏的细胞内寄生虫。此外，这些结果还表明了用于将所需试剂快速细胞内递送至巨噬细胞以用于各种目的的一般方法的可行性。
Methotrexate (Mtx) conjugated with maleylated bovine serum albumin (Mtx-MBSA) was taken up and degraded by cultured hamster peritoneal macrophages through the polyanion binding site for acetylated low density lipoprotein. Mtx-MBSA also eliminated intracellular amastigotes of Leishmania donovani in cultured hamster peritoneal macrophages about three times more efficiently than free Mtx. The antileishmanial effect of Mtx-MBSA on parasitized macrophages was blocked by MBSA, lysosomal inhibitors (chloroquine and monensin), and metabolic antagonists of Mtx (folic and folinic acids). The primary sites of accumulation of radioactivity of injected 125I-labeled Mtx-MBSA were the macrophage rich tissues, viz. liver and spleen. These results suggest that Mtx-MBSA would ensure rapid and effective killing of intracellular parasites harbored by macrophages. Furthermore, these results also indicate the feasibility of a general approach for rapid intracellular delivery of desired agents to macrophages for various purposes.