Moorjani M, Lejeune A, Gicquaud C, Lacroix J, Poyet P, Gaudreault R C
Département de Chimie-Biologie, Université du Québec à Trois-Rivières, Canada.
Anticancer Res. 1996 Sep-Oct;16(5A):2831-6.
We have recently developed a new drug which is a carrier from red blood cell membrane. This carrier, named nanoerythrosome (nEryt), is prepared by extrusion of erythrocyte ghosts to produce small vesicles having an average diameter of 100 nm. Daunorubicin (DNR) was covalently conjugated to the nEryt (nEryt-DNR) using glutaraldehyde as homobifunctional linking arm. This led to a complex that is more active than free DNR both in vitro and in vivo. In this study, we identified the mechanisms that make the complex nEryt-DNR more active than free DNR. Using fluorescence microscopy and cellular-uptake, we observed that the nEryt-DNR complex cannot diffuse through the cell membrane and do not enter the cell by endocytosis. Our results suggest that the nEryt-DNR is rapidly absorbed onto the cell membrane. Free DNR is then slowly released by hydrolysis of the glutaraldehyde linking arm, producing a high concentration of free DNR in the cell's vicinity over a long period of time.
我们最近研发了一种新型药物，它是一种源自红细胞膜的载体。这种载体名为纳米红细胞体（nEryt），是通过挤压红细胞影体制备而成的小囊泡，平均直径为100纳米。使用戊二醛作为同双功能连接臂，将柔红霉素（DNR）共价连接到nEryt上（nEryt-DNR）。这产生了一种在体外和体内都比游离DNR更具活性的复合物。在本研究中，我们确定了使nEryt-DNR复合物比游离DNR更具活性的机制。通过荧光显微镜和细胞摄取，我们观察到nEryt-DNR复合物不能扩散穿过细胞膜，也不会通过内吞作用进入细胞。我们的结果表明，nEryt-DNR会迅速吸附到细胞膜上。然后，游离DNR通过戊二醛连接臂的水解缓慢释放，在很长一段时间内，在细胞附近产生高浓度的游离DNR。
