In vitro cytotoxicities and in vivo distribution of transferrin-platinum(II) complex

In vitro cytotoxic studies of protein-bound cis-diamminedichloroplatinum(II) (CDDP) against human epidermoid carcinoma A431 cells showed that transferrin (Tf)-bound CDDP (Tf-Pt, Pt/Tf 7:1 mol/mol), and human serum albumin (HSA)-bound CDDP (HSA-Pt, Pt/HSA 7:1 mol/mol) exerted antiproliferating activities with IC50 values of 7.2 and 85 microM, respectively. Tf-Pt inhibited the binding of 0.2 nM 125I-labeled human diferric transferrin (hTf(Fe)2) to A431 cells with a inhibition constant (Ki) of 42 nM, whereas HSA-Pt did not. In vivo distribution studies showed that hTf(Fe)2, the Ki of which was 5.3 nM to mouse melanoma B16 cells, was eliminated from plasma biexponentially in the B16-bearing and control mice after intravenous injection at a dose of 87 mg/kg, and AUCplasma values were 29 and 39 mg.h/mL, respectively. In the B16-bearing mice the AUCtumor 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 administration of the complex. In conclusion, Tf could be a promising carrier protein for the transport of Pt to tumors.