Journal
CANCER GENE THERAPY
Volume 8, Issue 10, Pages 783-787Publisher
NATURE PUBLISHING GROUP
DOI: 10.1038/sj.cgt.7700362
Keywords
tumor targeting; peptide vector; histidylated oligolysine; RGD motif
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We have developed a potential tumor-targeting peptide vector (cRGD-hK) that is intended to be systemically and repeatedly administered to patients with advanced solid tumors. The peptide vector of 36 L-amino acid residues, CRGDCF(K[H-IKKK)(6), comprises a tumor-homing RGD motif, a DNA-binding oligolysine, and histidyl residues to facilitate the delivery into the cytosol. Using cytomegalovirus-driven luciferase expression plasmids as a reporter, we tested the transfection efficiency of cRGD-hK in hepatoma and pancreatic cancer cell lines. Transfection with the cRGD-hK/plasmid complexes (molar ratio 4000:1) was inhibited by 50 nM bafilomycin A(1), an inhibitor of the vacuolar ATPase endosomal proton pump, or 10 muM cycloRGDfV, an integrin alphav beta3 antagonist, indicating that the three elements of cRGD-hK could function as expected, at least in vitro. In nude mice bearing tumors created by subcutaneous inoculation, luciferase activity in the tumor tissues 48 hours after the injection of the cRGD-hK/plasmid complexes through the tail vein (20 mug plasmids per mouse) was significantly higher than that in the lung, kidney, and spleen, but only slightly higher than that in the liver. Although the latter difference was small, we propose a potential nonviral gene therapy for advanced solid turners through use of the tumor-targeting peptide vector.
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