In vivo cancer targeting of water-soluble taxol by folic acid immobilization

Abstract

Previously, folic acid receptor-targeted Dextran-Taxol-Folic acid (Dex-TXL-FA) has shown the in vitro superior and selective antitumor activity against human oral cancer cell line (KB) compared with the absent of folic acid, Dextran-Taxol. Present study is given for further investigation of in vivo antitumor efficacy of Dex-TXL-FA in the murine tumor xenograft model. To evaluate the antitumor effect of taxol, tumor bearing mice were prepared by s.c. inoculation of 1.0 × 106 KB cells in the back of nude mice. Seven days after inoculation, the administration of saline, paclitaxel for injection (PTX), Dex-TXL, FA-adsorbed Dex-TXL and Dex-TXL-FA (covalent) was started at a dose of 10mg/kg, by i.v. injection via the lateral tail vein three times (on day 7, 9, and 11) and animal survival rate and tumor sizes were monitored.FA-adsorbed Dex-TXL and Dex-TXL-FA (covalent) showed approximately 3 times greater anticancer effect than that of taxol at the 30th day after tumor implantation. Furthermore, these FA immobilized TXL showed 2-3 month longer animal survival than that of taxol. These results suggest the conjugation with Dex and FA could provide an improvement in the anticancer therapy of taxol. © 2011 Nakamura J, et al.