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Noninvasive detection of macrophages in atherosclerotic lesions by computed tomography enhanced with PEGylated gold nanoparticles.

Qin J, Peng C, Zhao B, Ye K, Yuan F, Peng Z, Yang X, Huang L, Jiang M, Zhao Q, Tang G, Lu X - Int J Nanomedicine (2014)

Bottom Line: In this study, dendrimer-entrapped gold nanoparticles (Au DENPs) with polyethylene glycol (PEG) and fluorescein isothiocyanate (FI) coatings were designed, tested, and applied as contrast agents for the enhanced computed tomography (CT) imaging of macrophages in atherosclerotic lesions.Cell counting kit-8 assay, fluorescence microscopy, silver staining, and transmission electron microscopy revealed that the FI-functionalized Au DENPs are noncytotoxic at high concentrations (3.0 μM) and can be efficiently taken up by murine macrophages in vitro.Our findings suggest that the designed PEGylated gold nanoparticles are promising biocompatible nanoprobes for the CT imaging of macrophages in atherosclerotic lesions and will provide new insights into the pathophysiology of AS and other concerned inflammatory diseases.

View Article: PubMed Central - PubMed

Affiliation: Department of Vascular Surgery, Shanghai Ninth People's Hospital Affiliated to Shanghai JiaoTong University, School of Medicine, Shanghai, People's Republic of China.

ABSTRACT
Macrophages are becoming increasingly significant in the progression of atherosclerosis (AS). Molecular imaging of macrophages may improve the detection and characterization of AS. In this study, dendrimer-entrapped gold nanoparticles (Au DENPs) with polyethylene glycol (PEG) and fluorescein isothiocyanate (FI) coatings were designed, tested, and applied as contrast agents for the enhanced computed tomography (CT) imaging of macrophages in atherosclerotic lesions. Cell counting kit-8 assay, fluorescence microscopy, silver staining, and transmission electron microscopy revealed that the FI-functionalized Au DENPs are noncytotoxic at high concentrations (3.0 μM) and can be efficiently taken up by murine macrophages in vitro. These nanoparticles were administered to apolipoprotein E knockout mice as AS models, which demonstrated that the macrophage burden in atherosclerotic areas can be tracked noninvasively and dynamically three-dimensionally in live animals using micro-CT. Our findings suggest that the designed PEGylated gold nanoparticles are promising biocompatible nanoprobes for the CT imaging of macrophages in atherosclerotic lesions and will provide new insights into the pathophysiology of AS and other concerned inflammatory diseases.

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CCK-8 assay of the viability of macrophages treated with different [(Au0)300-G5.NHAc-FI-mPEG] DENP concentrations for 24 hours (n=4).Abbreviations: CCK-8, cell counting kit-8; DENP, dendrimer-entrapped gold nanoparticle; FI, fluorescein isothiocyanate; PEG, polyethylene glycol.
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f4-ijn-9-5575: CCK-8 assay of the viability of macrophages treated with different [(Au0)300-G5.NHAc-FI-mPEG] DENP concentrations for 24 hours (n=4).Abbreviations: CCK-8, cell counting kit-8; DENP, dendrimer-entrapped gold nanoparticle; FI, fluorescein isothiocyanate; PEG, polyethylene glycol.

Mentions: The CCK-8 assay showed that Ana-1 cells incubated with different Au concentrations (100–300 μM) have similar cell viabilities (as high as 90%) as the untreated control cells (P>0.05, n=4; Figure 4). Relative cell viability was only slightly affected up to an Au concentration of 400 μM (Figure 4). The nontoxicity of the Au DENPs up to 300 μM Au demonstrates that PEGylation modification greatly improves the biocompatibility of [(Au0)300-G5.NHAc-FI-mPEG] DENPs.


Noninvasive detection of macrophages in atherosclerotic lesions by computed tomography enhanced with PEGylated gold nanoparticles.

Qin J, Peng C, Zhao B, Ye K, Yuan F, Peng Z, Yang X, Huang L, Jiang M, Zhao Q, Tang G, Lu X - Int J Nanomedicine (2014)

CCK-8 assay of the viability of macrophages treated with different [(Au0)300-G5.NHAc-FI-mPEG] DENP concentrations for 24 hours (n=4).Abbreviations: CCK-8, cell counting kit-8; DENP, dendrimer-entrapped gold nanoparticle; FI, fluorescein isothiocyanate; PEG, polyethylene glycol.
© Copyright Policy
Related In: Results  -  Collection

License
Show All Figures
getmorefigures.php?uid=PMC4260660&req=5

f4-ijn-9-5575: CCK-8 assay of the viability of macrophages treated with different [(Au0)300-G5.NHAc-FI-mPEG] DENP concentrations for 24 hours (n=4).Abbreviations: CCK-8, cell counting kit-8; DENP, dendrimer-entrapped gold nanoparticle; FI, fluorescein isothiocyanate; PEG, polyethylene glycol.
Mentions: The CCK-8 assay showed that Ana-1 cells incubated with different Au concentrations (100–300 μM) have similar cell viabilities (as high as 90%) as the untreated control cells (P>0.05, n=4; Figure 4). Relative cell viability was only slightly affected up to an Au concentration of 400 μM (Figure 4). The nontoxicity of the Au DENPs up to 300 μM Au demonstrates that PEGylation modification greatly improves the biocompatibility of [(Au0)300-G5.NHAc-FI-mPEG] DENPs.

Bottom Line: In this study, dendrimer-entrapped gold nanoparticles (Au DENPs) with polyethylene glycol (PEG) and fluorescein isothiocyanate (FI) coatings were designed, tested, and applied as contrast agents for the enhanced computed tomography (CT) imaging of macrophages in atherosclerotic lesions.Cell counting kit-8 assay, fluorescence microscopy, silver staining, and transmission electron microscopy revealed that the FI-functionalized Au DENPs are noncytotoxic at high concentrations (3.0 μM) and can be efficiently taken up by murine macrophages in vitro.Our findings suggest that the designed PEGylated gold nanoparticles are promising biocompatible nanoprobes for the CT imaging of macrophages in atherosclerotic lesions and will provide new insights into the pathophysiology of AS and other concerned inflammatory diseases.

View Article: PubMed Central - PubMed

Affiliation: Department of Vascular Surgery, Shanghai Ninth People's Hospital Affiliated to Shanghai JiaoTong University, School of Medicine, Shanghai, People's Republic of China.

ABSTRACT
Macrophages are becoming increasingly significant in the progression of atherosclerosis (AS). Molecular imaging of macrophages may improve the detection and characterization of AS. In this study, dendrimer-entrapped gold nanoparticles (Au DENPs) with polyethylene glycol (PEG) and fluorescein isothiocyanate (FI) coatings were designed, tested, and applied as contrast agents for the enhanced computed tomography (CT) imaging of macrophages in atherosclerotic lesions. Cell counting kit-8 assay, fluorescence microscopy, silver staining, and transmission electron microscopy revealed that the FI-functionalized Au DENPs are noncytotoxic at high concentrations (3.0 μM) and can be efficiently taken up by murine macrophages in vitro. These nanoparticles were administered to apolipoprotein E knockout mice as AS models, which demonstrated that the macrophage burden in atherosclerotic areas can be tracked noninvasively and dynamically three-dimensionally in live animals using micro-CT. Our findings suggest that the designed PEGylated gold nanoparticles are promising biocompatible nanoprobes for the CT imaging of macrophages in atherosclerotic lesions and will provide new insights into the pathophysiology of AS and other concerned inflammatory diseases.

Show MeSH
Related in: MedlinePlus