| Abstract: | The purpose of our study was to develop and evaluate a novel integrin αvβ3‐specific delivery carrier for transfection of siRNA in malignant tumors. We adopted arginine‐glycine‐aspartate (RGD) motif as a tissue target for specific recognition of integrin ανβ3. A chimaeric peptide was synthesized by adding nonamer arginine residues (9‐arginine [9R]) at the carboxy terminus of cyclic‐RGD dimer, designated as c(RGD)2‐9R, to enable small interfering RNA (siRNA) binding. To test the applicability of the delivery carrier in vivo, c(RGD)2‐9R was labeled with radionuclide of technetium‐99m. Biodistribution and γ‐camera imaging studies were performed in HepG2 xenograft‐bearing nude mice. As results, an optimal 10:1 molar ratio of 99mTc‐c(RGD)2‐9R to siRNA was indicated by the electrophoresis on agarose gels. 99mTc‐c(RGD)2‐9R/siRNA remained stable under a set of conditions in vitro. For in vivo study, tumor radioactivity uptake of 99mTc‐c(RGD)2‐9R/siRNA in nude mice bearing HepG2 xenografts was significantly higher than that of control probe (P < .05). The xenografts were clearly visualized at 4 hours till 6 hours noninvasively after intravenous injection of 99mTc‐c(RGD)2‐9R/siRNA, while the xenografts were not visualized at any time after injection of control probe. It was concluded that c(RGD)2‐9R could be an effective siRNA delivery carrier. Technetium‐99m radiolabeled‐delivery carrier represents a potential imaging strategy for RNAi‐based therapy. |
