Labeling monocytes with gold nanoparticles to track their recruitment in atherosclerosis with computed tomography

Abstract

Monocytes are actively recruited from the circulation into developing atherosclerotic plaques. In the plaque, monocytes differentiate into macrophages and eventually form foam cells. Continued accumulation of foam cells can lead to plaque rupture and subsequent myocardial infarction. X-ray computed tomography (CT) is the best modality to image the coronary arteries non-invasively, therefore we have sought to track the accumulation of monocytes into atherosclerotic plaques using CT. Gold nanoparticles were synthesized and stabilized with a variety of ligands. Select formulations were incubated with an immortalized monocyte cell line in vitro and evaluated for cytotoxicity, effects on cytokine release, and cell uptake. These data identified a lead formulation, 11-MUDA capped gold nanoparticles, to test for labeling primary monocytes. The formulation did not the affect the viability or cytokine release of primary monocytes and was highly taken up by these cells. Gold labeled primary monocytes were injected into apolipoprotein E deficient mice kept on Western diet for 10 weeks. Imaging was done with a microCT scanner. A significant increase in attenuation was measured in the aorta of mice receiving the gold labeled cells as compared to control animals. Following the experiment, the biodistribution of gold was evaluated in major organs. Additionally, plaques were sectioned and examined with electron microscopy. The results showed that gold nanoparticles were present inside monocytes located within plaques. This study demonstrates the feasibility of using gold nanoparticles as effective cell labeling contrast agents for non-invasive imaging of monocyte accumulation within plaques with CT.

PEGylated Polyethylenimine-Entrapped Gold Nanoparticles Loaded With Gadolinium For Dual-Mode Ct/Mr Imaging Applications

“…A wide variety of NPs have been utilized as contrast agents for x-ray computed tomography (CT) [6][7][8][9], magnetic resonance (MR) [10][11][12][13][14][15], positron emission tomography [16,17] and fluorescence imaging [18][19][20] etc. as they can improve the accuracy and sensitivity of medical diagnosis.…”

“…as they can improve the accuracy and sensitivity of medical diagnosis. For example, citrate-stabilized Au NPs functionalized with 11-mercaptoundecanoic acid displayed low cytotoxicity and high uptake in monocytes, which can be used for tracking the recruitment of monocytes in atherosclerosis via CT imaging [7]. Bi 2 S 3 nanorods [21] or nanodots [22] with surface modified by polyethylene glycol (PEG) can be used for CT imaging of blood pool or liver.…”

Gold nanoparticles enlighten the future of cancer theranostics

“…52 For example, cationic surfactant-free AuNPs (~2-200 nm) have been developed that were synthesized in water using a seed growth method, in the presence of l-cysteine methyl ester hydrochloride (HSCH 2 CH(NH 2 )COOCH 3 ⋅HCl) as a capping agent. 53 Furthermore, Chhour et al 54 have functionalized AuNPs using a group of thiol and amine ligands, including 11-mercaptoundecanoic acid (11-MUDA), 16-mercaptohexadecanoic acid (16-MHDA), polyethylenimine (PEI), 4-mercapto-1-butanol (4-MB), and 11-mercaptoundecyltetra (ethylene glycol) (MTEG). These ligands enhanced the AuNP stability and provided different surface functionalities which can influence cell uptake and cytotoxicity.…”

“…54 Among them, the 11-MUDA AuNPs were used to monitor the recruitment of monocytes into atherosclerotic plaques in a disease mouse model using X-ray computed tomography (CT), potentially allowing detection of monocyte recruitment in the presence of emerging atherosclerosis therapies. 54 In addition, Liu et al 55 have recently stabilized AuNPs using thiol-polyethylene glycol (SH-PEG) at two different ratios of thiol to PEG (1:1 and 1:2), significantly improving the AuNP stability in biological media. When AuNPs with higher PEG content were intravenously injected, they were found to accumulate in the liver at a lower level relative to counterparts with lower PEG content.…”

Gold Nanoparticles as X-Ray, CT, and Multimodal Imaging Contrast Agents: Formulation, Targeting, and Methodology

“…These particles were used to label monocytes ex vivo before injection into atherosclerotic mice. Over the course of 5 days, CT signal at the aorta increased significantly pointing to an accumulation of AuNP and therefore the macrophages [78].…”