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 ...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.展开更多
MR imaging of gene transcription is important as it should enable the non-invasive detection of mRNA alterations in disease. A range of MRI methods have been proposed for in vivo molecular imaging of cells based on th...MR imaging of gene transcription is important as it should enable the non-invasive detection of mRNA alterations in disease. A range of MRI methods have been proposed for in vivo molecular imaging of cells based on the use of ultra- small super-paramagnetic iron oxide (USPIO) nanoparticles and related susceptibility weighted imaging methods. Al-though immunohistochemistry can robustly differentiate the expression of protein variants, there is currently no direct gene assay technique that is capable of differentiating established to differentiate the induction profiles of c-Fos mRNA in vivo. To visualize the differential FosB gene expression profile in vivo after burn trauma, we developed MR probes that link the T2* contrast agent [superparamagnetic iron oxide nanoparticles (SPION)] with an oligodeoxynucleotide (ODN) sequence complementary to FosB mRNA to visualize endogenous mRNA targets via in vivo hybridization. The presence of this SPION-ODN probe in cells results in localized signal reduction in T2*-weighted MR images, in which the rate of signal reduction (R2*) reflects the regional iron concentration at different stages of amphetamine (AMPH) exposure in living mouse tissue. Our aim was to produce a superior contrast agent that can be administered using sys- temic as opposed to local administration and which will target and accumulate at sites of burn injury. Specifically, we developed and evaluated a PEGylated lipid coated MR probe with ultra-small super-paramagnetic iron oxide nanoparti- cles (USPION, a T2 susceptibility agent) coated with cationic fusogenic lipids, used for cell transfection and gene de- livery and covalently linked to a phosphorothioate modified oligodeoxynucleotide (sODN) complementary to c-Fos mRNA (SPION-cFos) and used the agent to image mice with leg burns. Our study demonstrated the feasibility of monitoring burn injury using MR imaging of c-Fos transcription in vivo, in a clinically relevant mouse model of burn injury for the first time.展开更多
基金Technical support from the Emory-Georgia Tech Nanotechnology Center for Personalizedsupported by the National High Technology Research and Development Program of China(2006AA02Z485)+2 种基金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)
文摘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.
文摘MR imaging of gene transcription is important as it should enable the non-invasive detection of mRNA alterations in disease. A range of MRI methods have been proposed for in vivo molecular imaging of cells based on the use of ultra- small super-paramagnetic iron oxide (USPIO) nanoparticles and related susceptibility weighted imaging methods. Al-though immunohistochemistry can robustly differentiate the expression of protein variants, there is currently no direct gene assay technique that is capable of differentiating established to differentiate the induction profiles of c-Fos mRNA in vivo. To visualize the differential FosB gene expression profile in vivo after burn trauma, we developed MR probes that link the T2* contrast agent [superparamagnetic iron oxide nanoparticles (SPION)] with an oligodeoxynucleotide (ODN) sequence complementary to FosB mRNA to visualize endogenous mRNA targets via in vivo hybridization. The presence of this SPION-ODN probe in cells results in localized signal reduction in T2*-weighted MR images, in which the rate of signal reduction (R2*) reflects the regional iron concentration at different stages of amphetamine (AMPH) exposure in living mouse tissue. Our aim was to produce a superior contrast agent that can be administered using sys- temic as opposed to local administration and which will target and accumulate at sites of burn injury. Specifically, we developed and evaluated a PEGylated lipid coated MR probe with ultra-small super-paramagnetic iron oxide nanoparti- cles (USPION, a T2 susceptibility agent) coated with cationic fusogenic lipids, used for cell transfection and gene de- livery and covalently linked to a phosphorothioate modified oligodeoxynucleotide (sODN) complementary to c-Fos mRNA (SPION-cFos) and used the agent to image mice with leg burns. Our study demonstrated the feasibility of monitoring burn injury using MR imaging of c-Fos transcription in vivo, in a clinically relevant mouse model of burn injury for the first time.
