IN-VITRO CYTOTOXICITIES AND IN-VIVO DISTRIBUTION OF TRANSFERRIN PLATINUM(II) COMPLEX

In vitro cytotoxic studies of protein-bound cis-diamminedichloroplatin um(II) (CDDP) against human epidermoid carcinoma A431 cells showed tha t transferrin (Tf)-bound CDDP (Tf-Pt, Pt/Tf 7:1 mol/mol), and human se rum albumin (HSA)-bound CDDP (HSA-Pt, Pt/HSA 7:1 mol/ mel) exerted ant iproliferating activities with IC50 values of 7.2 and 85 mu M, respect ively. Tf-Pt inhibited the binding of 0.2 nM I-125-labeled human difer ric transferrin (hTf(Fe)(2)) to A431 cells with a inhibition constant (K-i) of 42 nM, whereas HSA-Pt did not. In vivo distribution studies s howed that hTf(Fe)(2), the K-i of which was 5.3 nM to mouse melanoma B 16 cells, was eliminated from plasma biexponentially in the B16-bearin g and control mice after intravenous injection at a dose of 87 mg/kg, and AUC(plasma) values were 29 and 39 mg.h/mL, respectively. In the B1 6-bearing mice the AUC(tumor) was 5.6 mg.h/mL, while the AUCs of liver , kidney, and spleen were not distinguishable between the B16-bearing and control mice. Subsequently Tf-Pt (Pt/Tf 3:1 mol/mol) and free CDDP solution were administered intravenously to the B16-bearing mice. The systemic circulation of Pt was significantly prolonged by the adminis tration of the complex. In conclusion, Tf could be a promising carrier protein for the transport of Pi to tumors.