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Merck
  • Macrophage-specific lipid-based nanoparticles improve cardiac magnetic resonance detection and characterization of human atherosclerosis.

Macrophage-specific lipid-based nanoparticles improve cardiac magnetic resonance detection and characterization of human atherosclerosis.

JACC. Cardiovascular imaging (2009-05-16)
Michael J Lipinski, Juan C Frias, Vardan Amirbekian, Karen C Briley-Saebo, Venkatesh Mani, Daniel Samber, Antonio Abbate, Juan Gilberto S Aguinaldo, Davis Massey, Valentin Fuster, George W Vetrovec, Zahi A Fayad
摘要

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. Gd-containing lipid-based NPs targeting macrophages have improved MR detection of murine atherosclerosis. 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. 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. 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.

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Sigma-Aldrich
巨噬细胞集落刺激因子 人, M-CSF, recombinant, expressed in E. coli, lyophilized powder, suitable for cell culture
Sigma-Aldrich
巨噬细胞集落刺激因子 人, M-CSF, recombinant, expressed in HEK 293 cells, suitable for cell culture