In Vitro Cytotoxicities and In Vivo Distribution of Transferrin–Platinum(II) Complex

Abstract

In vitrocytotoxic studies of protein‐boundcis‐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 IC50values of 7.2 and 85 µM, respectively. Tf‐Pt inhibited the binding of 0.2 nM125I‐labeled human diferric transferrin (hTf(Fe)2) to A431 cells with a inhibition constant (Ki) of 42 nM, whereas HSA‐Pt did not.In vivodistribution studies showed that hTf(Fe)2theKiof 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 AUCplasmavalues were 29 and 39 mg·h/mL, respectively. In the B16‐bearing mice the AUCtumorwas 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.