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RGD-conjugated human ferritin nanoparticles for imaging vascular inflammation and angiogenesis in experimental carotid and aortic disease.

ABSTRACT: PURPOSE:Inflammation and angiogenesis are important contributors to vascular disease. We evaluated imaging both of these biological processes, using Arg-Gly-Asp (RGD)-conjugated human ferritin nanoparticles (HFn), in experimental carotid and abdominal aortic aneurysm (AAA) disease. PROCEDURES:Macrophage-rich carotid lesions were induced by ligation in hyperlipidemic and diabetic FVB mice (n?=?16). AAAs were induced by angiotensin II infusion in apoE(-/-) mice (n=10). HFn, with or without RGD peptide, was labeled with Cy5.5 and injected intravenously for near-infrared fluorescence imaging. RESULTS:RGD-HFn showed significantly higher signal than HFn in diseased carotids and AAAs relative to non-diseased regions, both in situ (carotid: 1.88?±?0.30 vs. 1.17?±?0.10, p?=?0.04; AAA: 2.59?±?0.24 vs. 1.82?±?0.16, p?=?0.03) and ex vivo. Histology showed RGD-HFn colocalized with macrophages in carotids and both macrophages and neoangiogenesis in AAA lesions. CONCLUSIONS:RGD-HFn enhances vascular molecular imaging by targeting both vascular inflammation and angiogenesis, and allows more comprehensive detection of high-risk atherosclerotic and aneurysmal vascular diseases.

SUBMITTER: Kitagawa T

PROVIDER: S-EPMC3963502 | biostudies-literature | 2012 Jun

REPOSITORIES: biostudies-literature

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RGD-conjugated human ferritin nanoparticles for imaging vascular inflammation and angiogenesis in experimental carotid and aortic disease.

Kitagawa Toshiro T Kosuge Hisanori H Uchida Masaki M Dua Monica M MM Iida Yasunori Y Dalman Ronald L RL Douglas Trevor T McConnell Michael V MV

Molecular imaging and biology 20120601 3

<h4>Purpose</h4>Inflammation and angiogenesis are important contributors to vascular disease. We evaluated imaging both of these biological processes, using Arg-Gly-Asp (RGD)-conjugated human ferritin nanoparticles (HFn), in experimental carotid and abdominal aortic aneurysm (AAA) disease.<h4>Procedures</h4>Macrophage-rich carotid lesions were induced by ligation in hyperlipidemic and diabetic FVB mice (n = 16). AAAs were induced by angiotensin II infusion in apoE(-/-) mice (n=10). HFn, with or ...[more]

PMID: 21638084

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Project description:Interaction of nanomaterials with the mammalian cells remains to be poorly understood at the molecular level. Here we report the first synthesis of hybrid nanomaterial termed phage mimetic nanorods (PMN’s) inspired from filamentous bacteriophage present in nature. We emulate filamentous bacteriophage structure by combining two separate nanoscale entities, one functionalized gold nanorods and the other is coat proteins isolated from filamentous bacteriophage obtained through landscape phage screening. Utilizing biochemical interactions between a phage-derived protein and functionalized gold nanorods, we synthesized novel phage mimetic nanorods. The resulting nanovectors showed excellent multi functional properties including target specificity, imaging and photo destruction ability in a model SKBR-3 breast cancer cells. In addition, to gain insight into the molecular interactions involved during internalization of PMNs by SKBR-3 cells, we performed gene expression profiling of cells exposed to PMNs as compared with naive cells. We identified 70 upregulated and 26 downregulated genes responding to PMNs. Heparin binding internalization was identified as most plausible mechanisms of PMNs entry. Members of Major Histocompatibility complex I (MHC class I) were activated by PMNs, leading to enhanced lysosome and proteasome activity. Seven members of poorly annotated G antigen family (GAGE) of genes were upregulated, and may represent novel mechanism of PMNs entry recognition by cells. In summary, we present a versatile technique of PMNs production as any protein isolated from phage libraries selected against any in vitro and in vivo cells can be used as a source to synthesize PMN’s. This study also opens new avenues to understand the role of nanomaterials at the molecular level. Investigate the effect of phage mimetic nanorods onto SKBT-3 cells Two groups were compared, three biological replicates each. One group was control cells and the other was test.

Dataset Information

RGD-conjugated human ferritin nanoparticles for imaging vascular inflammation and angiogenesis in experimental carotid and aortic disease.

Publications

RGD-conjugated human ferritin nanoparticles for imaging vascular inflammation and angiogenesis in experimental carotid and aortic disease.

Similar Datasets

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