Faulk W P, Harats H, McIntyre J A, Berczi A, Sun I L, Crane F L
Center for Reproduction and Transplantation Immunology, Methodist Hospital of Indiana, Indianapolis 46202.
Am J Reprod Immunol. 1989 Nov-Dec;21(3-4):151-4. doi: 10.1111/j.1600-0897.1989.tb01021.x.
Cancer research in drug targeting has focused on the use of monoclonal antibody conjugates of drugs. This paper discusses the use of ligand conjugates of drugs to deliver to receptors on cancer cells. We have used transferrin coupled to adriamycin, and report these conjugates specifically bind and kill cancer cells in culture. Our studies of the mechanism show targeted plasma membranes are compromised for NADH ferricyanide reduction, and targeted cells lose diferric transferrin reductase activity. These results indicate that the binding of transferrin-adriamycin conjugates to transferrin receptors on either isolated plasma membranes or viable tumor cells causes an inhibition of redox reactions that are essential for growth. Since transferrin receptors are endocytosable, ligand-drug conjugates also are delivered to the interior of targeted cells where other mechanisms of killing can be employed. This novel method of drug delivery circumvents the need for monoclonal antibodies, and more investigation of the system may allow a controlled clinical study of its effectiveness.
药物靶向的癌症研究主要集中在药物的单克隆抗体偶联物的应用上。本文讨论了药物的配体偶联物用于递送至癌细胞上的受体的情况。我们使用了与阿霉素偶联的转铁蛋白，并报道这些偶联物在培养物中能特异性结合并杀死癌细胞。我们对作用机制的研究表明，靶向的质膜在还原铁氰化镍的过程中受到损害，且靶向细胞失去双铁转铁蛋白还原酶活性。这些结果表明，转铁蛋白 - 阿霉素偶联物与分离的质膜或活肿瘤细胞上的转铁蛋白受体结合会抑制对生长至关重要的氧化还原反应。由于转铁蛋白受体可被内吞，配体 - 药物偶联物也会被递送至靶向细胞内部，在此可采用其他杀伤机制。这种新型药物递送方法无需单克隆抗体，对该系统进行更多研究可能会使其有效性得到可控的临床研究。
