TY - JOUR
T1 - Macrophage-Specific Lipid-Based Nanoparticles Improve Cardiac Magnetic Resonance Detection and Characterization of Human Atherosclerosis
AU - Lipinski, Michael J.
AU - Frias, Juan C.
AU - Amirbekian, Vardan
AU - Briley-Saebo, Karen C.
AU - Mani, Venkatesh
AU - Samber, Daniel
AU - Abbate, Antonio
AU - Aguinaldo, Juan Gilberto S.
AU - Massey, Davis
AU - Fuster, Valentin
AU - Vetrovec, George W.
AU - Fayad, Zahi A.
N1 - Funding Information:
This study was supported in part by NIH/NHLBI ROI HL71021, NIH/NHLBI HL078667 (to Dr. Fayad), and the Stanley J. Sarnoff Endowment for Cardiovascular Research, Inc. (to Dr. Amirbekian). The MSSM-Microscopy Shared Resource Facility is supported by funding from NIH-NCI shared resources Grant R24 CA095823, and NSF Major Research Instrumentation Grant DBI-9724504.
PY - 2009/5
Y1 - 2009/5
N2 - 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-1s-1 at 1.5-T and 37°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.
AB - 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-1s-1 at 1.5-T and 37°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.
KW - CD36
KW - atherosclerosis
KW - macrophage
KW - magnetic resonance imaging
KW - nanoparticles
UR - http://www.scopus.com/inward/record.url?scp=65549128771&partnerID=8YFLogxK
U2 - 10.1016/j.jcmg.2008.08.009
DO - 10.1016/j.jcmg.2008.08.009
M3 - Article
C2 - 19442953
AN - SCOPUS:65549128771
SN - 1936-878X
VL - 2
SP - 637
EP - 647
JO - JACC: Cardiovascular Imaging
JF - JACC: Cardiovascular Imaging
IS - 5
ER -