Ho Y K, Mayhew E, Preisler H D, Bardos T J
Cancer Res. 1982 May;42(5):1740-3.
Partially thiolated polycytidylic acid (MPC), an antileukemic agent, when administered to leukemic RF/UN mice inhibited the clonogenicity of bone marrow progenitor cells in a time- and dose-dependent manner. The effect of a single dose of MPC disappeared within 40 hr due to the rapid degradation of this compound in mice. When MPC was encapsulated in liposomes before injection, its activity at 19 hr after inoculation was similar to that of free MPC. The inhibitory effect of this liposome-MPC complex, however, persisted for at least 40 hr, indicating that the MPC was protected from hydrolysis by the nucleases present in blood. Drug-free liposomes increased the number of clonogenic progenitor cells, whereas a mixture of plain liposomes and MPC decreased the number of clonogenic cells to a greater extent than did MPC alone or MPC within liposomes. A possible explantation for these observations is that the liposomes per se altered the clearance function of the reticuloendothelial system and completed with MPC for uptake by the reticuloendothelial system cells, thereby resulting in increased plasma levels of MPC which in turn resulted in greater killing of the target cells.
部分硫醇化聚胞苷酸（MPC）是一种抗白血病药物，给白血病RF/UN小鼠用药时，它以时间和剂量依赖的方式抑制骨髓祖细胞的克隆形成能力。由于该化合物在小鼠体内迅速降解，单剂量MPC的作用在40小时内消失。注射前将MPC包封在脂质体中时，接种后19小时其活性与游离MPC相似。然而，这种脂质体-MPC复合物的抑制作用至少持续40小时，这表明MPC受到血液中核酸酶水解的保护。不含药物的脂质体增加了克隆形成祖细胞的数量，而普通脂质体和MPC的混合物比单独的MPC或脂质体内的MPC更大程度地减少了克隆形成细胞的数量。对这些观察结果的一种可能解释是，脂质体本身改变了网状内皮系统的清除功能，并与MPC竞争被网状内皮系统细胞摄取，从而导致MPC血浆水平升高，进而导致对靶细胞的更大杀伤。
