In vivo tumor targeting imaging of cyclic RGD-modified heparin derivative to αvβ3-integrin expressing tumor

초록

Therapeutic target for over-expressed αvβ3 integrins in angiogenic endothelial cells and tumors is one of the promising approaches for cancer imaging and therapy. In the previous study, we demonstrated that heparin-lithocholic acid functionalized with cyclic RGDyK (cRGD-HL) had potent angiogenesis inhibition and tumor regression effects. The aim of this study is to validate the targeting property and specificity of cRGD-HL to αvβ3 integrin-expressing endothelial cells and tumor tissues by Cy5. 5-labeled cRGDyK (RGD-Cy5. 5) as αvβ3 integrin imaging agent and near-infrared fluorescence (NIRF) imaging systems. In this study, we demonstrated that cRGD-HL markedly inhibited the binding of fluorescein-labeled αvβ3 antibody to αvβ3 integrin-expressing endothelial cells when compared to non-functionalized heparin derivatives. Furthermore, in vivo NIRF images showed that cRGD-HL could decrease the NIRF signal intensities in both αvβ3 integrin-positive tumor (U87 MG) and αvβ3 integrin-negative tumor (SCC7) more effectively than non-functionalized heparin derivatives could. Therefore, with the help of αvβ3 integrin imaging agent and NIRF imaging systems, we verified that the functionalized cRGD-HL has much stronger tumor targeting property and specificity against αvβ3 integrin-expressing endothelial cells and tumors than non-functionalized heparin derivatives. Also, we believe that cRGD-HL will be useful and give affirmative outcomes for the treatment of angiogenesis-related diseases. © 2012 The Korean Society of Pharmaceutical Sciences and Technology and Springer Dordrecht.

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