T. Hoshino et al., IN-VITRO CYTOTOXICITIES AND IN-VIVO DISTRIBUTION OF TRANSFERRIN PLATINUM(II) COMPLEX, Journal of pharmaceutical sciences, 84(2), 1995, pp. 216-221
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.