Macrophage-specific lipid-based nanoparticles improve cardiac magnetic resonance detection and characterization of human atherosclerosis.
OBJECTIVE
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.
Lipinski
Michael J
MJ
Translational and Molecular Imaging Institute, Mount Sinai Medical Center, New York, New York, USA.
Frias
Juan C
JC
Amirbekian
Vardan
V
Briley-Saebo
Karen C
KC
Mani
Venkatesh
V
Samber
Daniel
D
Abbate
Antonio
A
Aguinaldo
Juan Gilberto S
JG
Massey
Davis
D
Fuster
Valentin
V
Vetrovec
George W
GW
Fayad
Zahi A
ZA
D001018:Aortic Diseases / Q000276:immunology / Q000473:pathology*; D050197:Atherosclerosis / Q000276:immunology / Q000473:pathology*; D001344:Autopsy; D001692:Biological Transport; D018955:CD36 Antigens / Q000378:metabolism; D002478:Cells, Cultured; D003287:Contrast Media / Q000378:metabolism; D006571:Heterocyclic Compounds / Q000378:metabolism; D006801:Humans; D007150:Immunohistochemistry; D008055:Lipids; D008264:Macrophages / Q000276:immunology / Q000473:pathology*; D008279:Magnetic Resonance Imaging; D018613:Microscopy, Confocal; D053758:Nanoparticles; D009942:Organometallic Compounds / Q000378:metabolism; D011237:Predictive Value of Tests; D013054:Spectrophotometry, Atomic
D018955:CD36 Antigens; D003287:Contrast Media; D006571:Heterocyclic Compounds; D008055:Lipids; D009942:Organometallic Compounds; C050823:gadolinium 1,4,7,10-tetraazacyclododecane-N,N',N'',N'''-tetraacetate