Macrophage-specific lipid-based nanoparticles improve cardiac magnetic resonance detection and characterization of human atherosclerosis.
JACC Cardiovasc Imaging
; 2(5): 637-47, 2009 May.
Article
en En
| MEDLINE
| ID: mdl-19442953
ABSTRACT
OBJECTIVES:
We sought to determine whether gadolinium (Gd)-containing lipid-based nanoparticles (NPs) targeting the macrophage scavenger receptor-B (CD36) improve cardiac magnetic resonance (CMR) detection and characterization of human atherosclerosis.BACKGROUND:
Gd-containing lipid-based NPs targeting macrophages have improved MR detection of murine atherosclerosis.METHODS:
Gadolinium-containing untargeted NPs, anti-CD36 NPs, and nonspecific Fc-NPs were created. Macrophages were incubated with fluorescent targeted and nontargeted NPs to determine uptake via confocal microscopy and inductively coupled plasma mass spectroscopy (ICP-MS) quantified Gd uptake. Human aortic specimens were harvested at autopsy. With a 1.5-T scanner, T1, T2, and PDW 3-dimensional scans were performed along with post-contrast scans after 24 h incubation. The T1 and cluster analyses were performed and compared with immunohistopathology.RESULTS:
The NPs had a mean diameter of 125 nm and 14,900 Gd-ions, and relaxivity was 37 mmol/l(-1)s(-1) at 1.5-T and 37 degrees C. Confocal microscopy and ICP-MS demonstrated significant in vitro macrophage uptake of targeted NPs, whereas non-targeted NPs had minimal uptake. On T1 imaging, targeted NPs increased contrast-to-noise ratio (CNR) by 52.5%, which was significantly greater than Fc-NPs (CNR increased 17.2%) and nontargeted NPs (CNR increased 18.7%) (p = 0.001). Confocal fluorescent microscopy showed that NPs target resident macrophages, whereas the untargeted NPs and Fc-NPs are found diffusely throughout the plaque. Targeted NPs had a greater signal intensity increase in the fibrous cap compared with non-targeted NPs.CONCLUSIONS:
Macrophage-specific (CD36) NPs bind human macrophages and improve CMR detection and characterization of human aortic atherosclerosis. Thus, macrophage-specific NPs could help identify high-risk human plaque before the development of an atherothrombotic event.
Texto completo:
1
Colección:
01-internacional
Base de datos:
MEDLINE
Asunto principal:
Compuestos Organometálicos
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Enfermedades de la Aorta
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Imagen por Resonancia Magnética
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Medios de Contraste
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Aterosclerosis
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Nanopartículas
/
Compuestos Heterocíclicos
/
Lípidos
/
Macrófagos
Tipo de estudio:
Diagnostic_studies
/
Prognostic_studies
Límite:
Humans
Idioma:
En
Revista:
JACC Cardiovasc Imaging
Asunto de la revista:
ANGIOLOGIA
/
CARDIOLOGIA
/
DIAGNOSTICO POR IMAGEM
Año:
2009
Tipo del documento:
Article
País de afiliación:
Estados Unidos