Vascular targeting is a novel strategy that directs endothelial toxins at
tumor vessels expressing specific markers and kills
tumor cells by vascular occlusion.
Integrin-binding RGD motif has been reported to have a homing property to experimental
tumor vasculature. In the present study, we evaluated the effect of vascular targeting by
doxorubicin-RGD-4C conjugate in an orthotopic murine
hepatoma model. MTT assay showed that dox-RGD-4C conjugates had lower cytotoxicity against MH134 mouse
hepatoma cells than free dox. When given intravenously to mice with implanted orthotopic
hepatoma, however, the dox-RGD-4C suppressed the growth of
hepatoma more effectively than free dox (mean
tumor volumes 24 mm(3) vs. 67 mm(3), respectively; p=0.047). Histologic analysis of the
hepatoma tissue revealed prominent
tumor cell death in the dox-RGD-4C treated group and complete
tumor cell
necrosis in 40% of cases. Immunochemical staining showed expression of
integrin alphav mainly around the
tumor nodule. These results show that
dox-RGD-4C conjugate has a better antitumor effect in an orthotopic mouse
hepatoma model by
tumor targeting.
Integrin alphav of
hepatoma feeding vessels is suggested to be targeted by the
dox-RGD-4C conjugate.