van Rooijen N, Kors N, ter Hart H, Claassen E
Department of Histology, Medical Faculty, Free University, Amsterdam, The Netherlands.
Virchows Arch B Cell Pathol Incl Mol Pathol. 1988;54(4):241-5. doi: 10.1007/BF02899217.
It is shown in the present study that RAW 264 tumor cells can be killed by liposome-entrapped dichloromethylene diphosphonate (DMDP), both in vitro and in vivo. DMDP is ingested by phagocytic cells when entrapped in liposomes. Once phagocytized the liposomal membranes are digested and the drug is released into the cell and is ready for action. In vitro, even low doses of liposome-entrapped DMDP caused an significant reduction in cell numbers. In vivo, liposome-encapsulated DMDP markedly reduced tumor formation in the liver, when given 1 day after injection of 1 x 10(6) RAW 264 tumor cells. Liposome-encapsulated DMDP, given 4 or more days after injection of the tumor cells had no significant effect. We concluded that tumor formation by RAW 264 cells is only susceptible to in vivo treatment with liposome-entrapped DMDP during a short period of time after injection of the cells. Obviously, phagocytosis of the tumor cells is reduced after this period making the cells less susceptible to treatment with the liposome-entrapped drug.
本研究表明，脂质体包裹的二氯亚甲基二膦酸盐（DMDP）在体外和体内均可杀死RAW 264肿瘤细胞。当DMDP包裹在脂质体中时，可被吞噬细胞摄取。一旦被吞噬，脂质体膜被消化，药物释放到细胞中并准备发挥作用。在体外，即使是低剂量的脂质体包裹的DMDP也会导致细胞数量显著减少。在体内，当在注射1×10(6)个RAW 264肿瘤细胞1天后给予脂质体包裹的DMDP时，可显著减少肝脏中的肿瘤形成。在注射肿瘤细胞4天或更长时间后给予脂质体包裹的DMDP则没有显著效果。我们得出结论，RAW 264细胞形成的肿瘤仅在注射细胞后的短时间内对脂质体包裹的DMDP体内治疗敏感。显然，在此期间后肿瘤细胞的吞噬作用降低，使得细胞对脂质体包裹药物的治疗敏感性降低。
