摘要
Integrin is often significantly up-regulated in activated endothelial cells during tumor angiogenesis.The arginine-glycine-aspartic acid(RGD)peptide sequence is a specific recognition motif toανβ3 integrin.In this study,a RGD labeled,Poly lactic acid(PLA) coated ultrasmall paramagnetic iron oxide(USPIO)(referred to as RGD-PLA-USPIO)were developed and the ability to detect tumor angiogenesis was investigated in vitro and in vivo.Increased uptake of RGD-PLA-USPIO by human umbilical vein endothelial cells(HUVECs)was detected by Prussian blue stain and transmission electronic microscopy(TEM).Pronounced signal decrease in T2*-weighted magnetic resonance image(MRI)and heterogeneous arrangement of neovasculature of tumor tissue were clearly identified in Vx-2 tumor model.The MR signal of contralateral muscle only could be seen a slight background change after either RGD-PLA-USPIO or PLA-USPIO injection.These studies demonstrate the efficiency of RGD-PLA-USPIO to visualizeανβ3 integrin in activated tumor endothelial cells and its potential for detecting and monitoring tumor vasculature change after therapy.
Integrin is often significantly up-regulated in activated endothelial cells during tumor angiogenesis. The arginine-glycine-aspartic acid （RGD） peptide sequence is a specific recognition motif to αvβ3 integrin. In this study, a RGD labeled, Poly lactic acid （PLA） coated ultrasmall paramagnetic iron oxide （USPIO） （referred to as RGD-PLA-USPIO） were developed and the ability to detect tumor angiogenesis was investigated in vitro and in vivo. Increased uptake of RGD-PLA-USPIO by human umbilical vein endothelial cells （HUVECs） was detected by Prussian blue stain and transmission electronic microscopy （TEM）. Pronounced signal decrease in T2^＊-weighted magnetic resonance image （MRI） and heterogeneous arrangement of neovasculature of tumor tissue were clearly identified in Vx-2 tumor model. The MR signal of contralateral muscle only could be seen a slight background change after either RGD-PLA-USPIO or PLA-USPIO injection. These studies demonstrate the efficiency of RGD-PLA-USPIO to visualize αvβ3 integrin in activated tumor endothelial cells and its potential for detecting and monitoring tumor vasculature change after therapy.
基金
Technical support from the Emory-Georgia Tech Nanotechnology Center for Personalized
supported by the National High Technology Research and Development Program of China(2006AA02Z485)
Specific Prevention and Control Technology for Major Disease of Zhejiang Province(2008C13027-2)
Natural Science Foundation of Zhejiang Province(J20060714)
Special Foundation for Young Scientists of Zhejiang Province(2009QN009)
