کد مقاله | کد نشریه | سال انتشار | مقاله انگلیسی | نسخه تمام متن |
---|---|---|---|---|
2065696 | 1076934 | 2008 | 11 صفحه PDF | دانلود رایگان |
![عکس صفحه اول مقاله: Generation of ammodytoxin-anti-cathepsin B immuno-conjugate as a model for delivery of secretory phospholipase A2 into cancer cells Generation of ammodytoxin-anti-cathepsin B immuno-conjugate as a model for delivery of secretory phospholipase A2 into cancer cells](/preview/png/2065696.png)
Ammodytoxin C (AtxC) is a toxic secreted phospholipase A2 (sPLA2) from the venom of Vipera ammodytes snake. To evaluate its potential to kill cancer cells, the toxin was cross-linked to the monoclonal antibody against cathepsin B which endocytoses upon binding to cathepsin B, an antigen overexpressed on the plasma membrane of cancer cells. A photo-reactive derivative of AtxC, possessing the same biological activity as the native toxin, was reacted with antibodies to form a covalent immuno-conjugate. In conditions of the cytosolic redox potential, AtxC was gradually released from the conjugate due to reduction of the disulfide bond in the spacer arm of the cross-linker. The phospholipase activity of the preparation reached maximum in 10 min and then decreased gradually. As demonstrated by fluorescence microscopy, the immuno-conjugate targeted Caco-2 colon adenocarcinoma cells but was very slowly internalized, the likely reason of only slight cytotoxicity being observed. Despite the lack of a clear cytotoxic effect of AtxC–antibody conjugate on Caco-2 cells, we demonstrated in this work a new methodology for the targeted delivery of (toxic) sPLA2 into cells, promising in research or therapy.
Journal: Toxicon - Volume 51, Issue 5, April 2008, Pages 754–764