Abstract
The drug delivery system using transferrin receptor mediated endocytosis is described. Transferrin is a serum glycoprotein which carries iron to cells possessing its receptor. The expression of transferrin receptor has been well known to be increased in cells with malignant transformation. Our aim is to utilize the transferrin-transferrin receptor system for the specific delivery of anticancer drugs and foreign genes. Human transferrin was conjugated with anticancer polypeptide, neocarzinostatin (NCS) by using (SPDP) and purified by ion exchange chromatography. The obtained Tf-NCS conjugate is capable binding to transferrin receptor and shows higher cytotoxicity. In vivo study using tumor inoculated mice also showed the significant growth suppression. The cytotoxicity of the conjugate was the sum of the receptor binding and intracellular degradation. Similar strategy was adopted to foreign gene transfer to tumor cells and IL-2 activated lymphocytes both of which express transferrin receptors. Transferrin was conjugated with vector containing β-galactosidase by transamination. The conjugate was effectively transferred to cells by receptor-mediated fashion and the transfected gene was expressed. This procedure would be useful for gene therapy.
