RGD targeting of human ferritin iron oxide nanoparticles enhances in vivo MRI of vascular inflammation and angiogenesis in experimental carotid disease and abdominal aortic aneurysm

Toshiro Kitagawa, Hisanori Kosuge, Masaki Uchida, Yasunori Iida, Ronald L. Dalman, Trevor Douglas, Michael V. McConnell

Research output: Contribution to journalArticle

11 Citations (Scopus)

Abstract

Purpose: To evaluate Arg-Gly-Asp (RGD)-conjugated human ferritin (HFn) iron oxide nanoparticles for in vivo magnetic resonance imaging (MRI) of vascular inflammation and angiogenesis in experimental carotid disease and abdominal aortic aneurysm (AAA). Materials and Methods: HFn was genetically engineered to express the RGD peptide and Fe3O4 nanoparticles were chemically synthesized inside the engineered HFn (RGD-HFn). Macrophage-rich left carotid lesions were induced by ligation in FVB mice made hyperlipidemic and diabetic (n = 14), with the contralateral right carotid serving as control. Murine AAAs were created by continuous angiotensin II infusion in ApoE-deficient mice (n = 12), while control mice underwent saline infusion (n = 8). All mice were imaged before and after intravenous injection with either RGD-HFn-Fe3O4 or HFn-Fe3O4 using a gradient-echo sequence on a whole-body 3T clinical scanner, followed by histological analysis. The nanoparticle accumulation was assessed by the extent of T* 2-induced carotid lumen reduction (% lumen loss) or aortic T* 2 -weighted signal intensity reduction (% SI [signal intensity] loss). Results: RGD-HFn-Fe3O4 was taken up more than HFn-Fe3O4 in both the ligated left carotid arteries (% lumen loss; 69 ± 9% vs. 36 ± 7%, P = 0.01) and AAAs (% SI loss; 47 ± 6% vs. 20 ± 5%, P = 0.01). The AAA % SI loss correlated positively with AAA size (r = 0.89, P < 0.001). Histology confirmed the greater accumulation and colocalization of RGD-HFn-Fe3O4 to both vascular macrophages and endothelial cells. Conclusion: RGD-HFn-Fe3O4 enhances in vivo MRI by targeting both vascular inflammation and angiogenesis, and provides a promising translatable MRI approach to detect high-risk atherosclerotic and aneurysmal vascular diseases. Level of Evidence: 1. J. Magn. Reson. Imaging 2017;45:1144–1153.

Original languageEnglish
Pages (from-to)1144-1153
Number of pages10
JournalJournal of Magnetic Resonance Imaging
Volume45
Issue number4
DOIs
Publication statusPublished - 2017 Apr 1
Externally publishedYes

Fingerprint

Abdominal Aortic Aneurysm
Ferritins
Nanoparticles
Blood Vessels
Magnetic Resonance Imaging
Inflammation
Macrophages
ferric oxide
Apolipoproteins E
Vascular Diseases
Carotid Arteries
Intravenous Injections
Angiotensin II
Ligation
Histology
Endothelial Cells

Keywords

  • aneurysms
  • angiogenesis
  • atherosclerosis
  • iron
  • nanoparticles
  • RGD

ASJC Scopus subject areas

  • Radiology Nuclear Medicine and imaging

Cite this

RGD targeting of human ferritin iron oxide nanoparticles enhances in vivo MRI of vascular inflammation and angiogenesis in experimental carotid disease and abdominal aortic aneurysm. / Kitagawa, Toshiro; Kosuge, Hisanori; Uchida, Masaki; Iida, Yasunori; Dalman, Ronald L.; Douglas, Trevor; McConnell, Michael V.

In: Journal of Magnetic Resonance Imaging, Vol. 45, No. 4, 01.04.2017, p. 1144-1153.

Research output: Contribution to journalArticle

Kitagawa, Toshiro ; Kosuge, Hisanori ; Uchida, Masaki ; Iida, Yasunori ; Dalman, Ronald L. ; Douglas, Trevor ; McConnell, Michael V. / RGD targeting of human ferritin iron oxide nanoparticles enhances in vivo MRI of vascular inflammation and angiogenesis in experimental carotid disease and abdominal aortic aneurysm. In: Journal of Magnetic Resonance Imaging. 2017 ; Vol. 45, No. 4. pp. 1144-1153.
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abstract = "Purpose: To evaluate Arg-Gly-Asp (RGD)-conjugated human ferritin (HFn) iron oxide nanoparticles for in vivo magnetic resonance imaging (MRI) of vascular inflammation and angiogenesis in experimental carotid disease and abdominal aortic aneurysm (AAA). Materials and Methods: HFn was genetically engineered to express the RGD peptide and Fe3O4 nanoparticles were chemically synthesized inside the engineered HFn (RGD-HFn). Macrophage-rich left carotid lesions were induced by ligation in FVB mice made hyperlipidemic and diabetic (n = 14), with the contralateral right carotid serving as control. Murine AAAs were created by continuous angiotensin II infusion in ApoE-deficient mice (n = 12), while control mice underwent saline infusion (n = 8). All mice were imaged before and after intravenous injection with either RGD-HFn-Fe3O4 or HFn-Fe3O4 using a gradient-echo sequence on a whole-body 3T clinical scanner, followed by histological analysis. The nanoparticle accumulation was assessed by the extent of T* 2-induced carotid lumen reduction ({\%} lumen loss) or aortic T* 2 -weighted signal intensity reduction ({\%} SI [signal intensity] loss). Results: RGD-HFn-Fe3O4 was taken up more than HFn-Fe3O4 in both the ligated left carotid arteries ({\%} lumen loss; 69 ± 9{\%} vs. 36 ± 7{\%}, P = 0.01) and AAAs ({\%} SI loss; 47 ± 6{\%} vs. 20 ± 5{\%}, P = 0.01). The AAA {\%} SI loss correlated positively with AAA size (r = 0.89, P < 0.001). Histology confirmed the greater accumulation and colocalization of RGD-HFn-Fe3O4 to both vascular macrophages and endothelial cells. Conclusion: RGD-HFn-Fe3O4 enhances in vivo MRI by targeting both vascular inflammation and angiogenesis, and provides a promising translatable MRI approach to detect high-risk atherosclerotic and aneurysmal vascular diseases. Level of Evidence: 1. J. Magn. Reson. Imaging 2017;45:1144–1153.",
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T1 - RGD targeting of human ferritin iron oxide nanoparticles enhances in vivo MRI of vascular inflammation and angiogenesis in experimental carotid disease and abdominal aortic aneurysm

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AU - Iida, Yasunori

AU - Dalman, Ronald L.

AU - Douglas, Trevor

AU - McConnell, Michael V.

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N2 - Purpose: To evaluate Arg-Gly-Asp (RGD)-conjugated human ferritin (HFn) iron oxide nanoparticles for in vivo magnetic resonance imaging (MRI) of vascular inflammation and angiogenesis in experimental carotid disease and abdominal aortic aneurysm (AAA). Materials and Methods: HFn was genetically engineered to express the RGD peptide and Fe3O4 nanoparticles were chemically synthesized inside the engineered HFn (RGD-HFn). Macrophage-rich left carotid lesions were induced by ligation in FVB mice made hyperlipidemic and diabetic (n = 14), with the contralateral right carotid serving as control. Murine AAAs were created by continuous angiotensin II infusion in ApoE-deficient mice (n = 12), while control mice underwent saline infusion (n = 8). All mice were imaged before and after intravenous injection with either RGD-HFn-Fe3O4 or HFn-Fe3O4 using a gradient-echo sequence on a whole-body 3T clinical scanner, followed by histological analysis. The nanoparticle accumulation was assessed by the extent of T* 2-induced carotid lumen reduction (% lumen loss) or aortic T* 2 -weighted signal intensity reduction (% SI [signal intensity] loss). Results: RGD-HFn-Fe3O4 was taken up more than HFn-Fe3O4 in both the ligated left carotid arteries (% lumen loss; 69 ± 9% vs. 36 ± 7%, P = 0.01) and AAAs (% SI loss; 47 ± 6% vs. 20 ± 5%, P = 0.01). The AAA % SI loss correlated positively with AAA size (r = 0.89, P < 0.001). Histology confirmed the greater accumulation and colocalization of RGD-HFn-Fe3O4 to both vascular macrophages and endothelial cells. Conclusion: RGD-HFn-Fe3O4 enhances in vivo MRI by targeting both vascular inflammation and angiogenesis, and provides a promising translatable MRI approach to detect high-risk atherosclerotic and aneurysmal vascular diseases. Level of Evidence: 1. J. Magn. Reson. Imaging 2017;45:1144–1153.

AB - Purpose: To evaluate Arg-Gly-Asp (RGD)-conjugated human ferritin (HFn) iron oxide nanoparticles for in vivo magnetic resonance imaging (MRI) of vascular inflammation and angiogenesis in experimental carotid disease and abdominal aortic aneurysm (AAA). Materials and Methods: HFn was genetically engineered to express the RGD peptide and Fe3O4 nanoparticles were chemically synthesized inside the engineered HFn (RGD-HFn). Macrophage-rich left carotid lesions were induced by ligation in FVB mice made hyperlipidemic and diabetic (n = 14), with the contralateral right carotid serving as control. Murine AAAs were created by continuous angiotensin II infusion in ApoE-deficient mice (n = 12), while control mice underwent saline infusion (n = 8). All mice were imaged before and after intravenous injection with either RGD-HFn-Fe3O4 or HFn-Fe3O4 using a gradient-echo sequence on a whole-body 3T clinical scanner, followed by histological analysis. The nanoparticle accumulation was assessed by the extent of T* 2-induced carotid lumen reduction (% lumen loss) or aortic T* 2 -weighted signal intensity reduction (% SI [signal intensity] loss). Results: RGD-HFn-Fe3O4 was taken up more than HFn-Fe3O4 in both the ligated left carotid arteries (% lumen loss; 69 ± 9% vs. 36 ± 7%, P = 0.01) and AAAs (% SI loss; 47 ± 6% vs. 20 ± 5%, P = 0.01). The AAA % SI loss correlated positively with AAA size (r = 0.89, P < 0.001). Histology confirmed the greater accumulation and colocalization of RGD-HFn-Fe3O4 to both vascular macrophages and endothelial cells. Conclusion: RGD-HFn-Fe3O4 enhances in vivo MRI by targeting both vascular inflammation and angiogenesis, and provides a promising translatable MRI approach to detect high-risk atherosclerotic and aneurysmal vascular diseases. Level of Evidence: 1. J. Magn. Reson. Imaging 2017;45:1144–1153.

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