Barabas K, Sizensky J A, Faulk W P
Center for Reproduction and Transplantation Immunology, Methodist Hospital of Indiana, Indianapolis 46202.
Am J Reprod Immunol. 1991 Apr;25(3):120-3. doi: 10.1111/j.1600-0897.1991.tb01078.x.
We have used transferrin-adriamycin conjugates to deliver drug to transferrin receptors and have shown that the conjugates bind to and kill tumor cells in vivo and in vitro. This has been studied with the use of qualitative and quantitative assays. In this report, we present evidence indicating that the primary target of transferrin-adriamycin cytotoxicity is the plasma membrane. This was done using a spectrofluorometric method that takes advantage of the fluorescence properties of adriamycin. It was shown that, while DNA intercalation may be the primary mechanism of cytotoxicity for free adriamycin, transferrin-adriamycin conjugates were not observed to interact with nuclear DNA. This may be a useful consideration in the design of future chemotherapeutic studies with transferrin conjugates of anticancer drugs.
我们已使用转铁蛋白-阿霉素偶联物将药物递送至转铁蛋白受体，并表明该偶联物在体内和体外均能结合并杀死肿瘤细胞。这已通过定性和定量测定进行了研究。在本报告中，我们提供的证据表明转铁蛋白-阿霉素细胞毒性的主要靶点是质膜。这是通过利用阿霉素的荧光特性的荧光分光光度法完成的。结果表明，虽然DNA嵌入可能是游离阿霉素细胞毒性的主要机制，但未观察到转铁蛋白-阿霉素偶联物与核DNA相互作用。这在未来设计抗癌药物转铁蛋白偶联物的化疗研究中可能是一个有用的考虑因素。
