Fibroblast growth factor receptors (FGFRs), overexpressed on the surface of a variety of
tumor cells and on
tumor neovasculature in situ, are potential targets for
tumor- and vascular-targeting
therapy. This study aimed to develop a FGFR-mediated drug delivery system to target chemotherapeutic agents to FGFR-overexpressed
tumor cells and
tumor neovasculature endothelial cells in vitro and in vivo. Here we designed a truncated human
basic fibroblast growth factor peptide (tbFGF), which was attached to the surface of cationic
liposomal doxorubicin (LPs-DOX) and
paclitaxel (LPs-PTX) via electrostatic force. Then we characterized the tbFGF-modified
liposome (tbFGF-LPs) and examined internalization of
doxorubicin in
tumor cells (TRAMP-C1, B16) and HUVEC cells in vitro. In vivo, we evaluated the biodistribution and antitumor efficacy of tbFGF-LPs-DOX and tbFGF-LPs-PTX in C57BL/6J mice bearing TRAMP-C1 prostate
carcinoma and
B16 melanoma, respectively. The tbFGF-LPs-DOX significantly improved the uptake of
doxorubicin in TRAMP-C1, B16 and HUVEC cells, respectively. Biodistribution study in B16
tumor-bearing mice showed that tbFGF-LPs-PTX achieved 7.1-fold (72.827+/-7.321mgh/L vs 10.292+/-0.775mgh/L, mean+/-SD, P<0.01) accumulation of
paclitaxel in
tumor tissue than those of free
paclitaxel. More importantly, treatment of
tumor-bearing mice with tbFGF-LPs-DOX and tbFGF-LPs-PTX showed the significant inhibition in
tumor growth and improvement in survival rate as compared with mice treated with free and liposomal drugs in TRAMP-C1 and B16
tumor models, respectively. Furthermore, repeated
intravenous administration of tbFGF-LPs-DOX/PTX did not induce anti-bFGF
antibodies. These results suggested that this FGFR-mediated drug delivery system may provide a new treatment strategy for
tumors which overexpress FGFRs.