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. 2018 May 24;10(2):62.
doi: 10.3390/pharmaceutics10020062.

Magnetic Nanoparticles Conjugated with Peptides Derived from Monocyte Chemoattractant Protein-1 as a Tool for Targeting Atherosclerosis

Chung-Wei Kao  1 , Po-Ting Wu  2 , Mei-Yi Liao  3 , I-Ju Chung  4 , Kai-Chien Yang  5 , Wen-Yih Isaac Tseng  6   7 , Jiashing Yu  8   9
Affiliations

Magnetic Nanoparticles Conjugated with Peptides Derived from Monocyte Chemoattractant Protein-1 as a Tool for Targeting Atherosclerosis

Chung-Wei Kao et al. Pharmaceutics. .

Abstract

Atherosclerosis is a multifactorial inflammatory disease that may progress silently for long period, and it is also widely accepted as the main cause of cardiovascular diseases. To prevent atherosclerotic plaques from generating, imaging early molecular markers and quantifying the extent of disease progression are desired. During inflammation, circulating monocytes leave the bloodstream and migrate into incipient lipid accumulation in the artery wall, following conditioning by local growth factors and proinflammatory cytokines; therefore, monocyte accumulation in the arterial wall can be observed in fatty streaks, rupture-prone plaques, and experimental atherosclerosis. In this work, we synthesized monocyte-targeting iron oxide magnetic nanoparticles (MNPs), which were incorporated with the peptides derived from the chemokine receptor C-C chemokine receptor type 2 (CCR2)-binding motif of monocytes chemoattractant protein-1 (MCP-1) as a diagnostic tool for potential atherosclerosis. MCP-1-motif MNPs co-localized with monocytes in in vitro fluorescence imaging. In addition, with MNPs injection in ApoE knockout mice (ApoE KO mice), the well-characterized animal model of atherosclerosis, MNPs were found in specific organs or regions which had monocytes accumulation, especially the aorta of atherosclerosis model mice, through in vivo imaging system (IVIS) imaging and magnetic resonance imaging (MRI). We also performed Oil Red O staining and Prussian Blue staining to confirm the co-localization of MCP-1-motif MNPs and atherosclerosis. The results showed the promising potential of MCP-1-motif MNPs as a diagnostic agent of atherosclerosis.

Keywords: MCP-1; atherosclerosis; iron oxide magnetic nanoparticle; monocytes.

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Conflict of interest statement

The authors declare no conflict of interest.

Figures

Figure 1
Figure 1
Scheme of the experiment.
Figure 2
Figure 2
Characterization of (a) magnetic nanoparticles (MNPs) and (b) monocytes chemoattractant protein-1 (MCP-1)-motif MNPs using TEM.
Figure 3
Figure 3
X-ray photoelectron spectroscopy (XPS) spectra of (a,c,e) MNPs and (b,d,f) MCP-1-motif MNPs.
Figure 4
Figure 4
M-H curve/hysteresis loop of iron oxide MNPs.
Figure 5
Figure 5
(a) MTT assay of 3T3 cells with different concentration of MCP-1-motif MNPs; (b–i) Live/Dead staining of WEHI 274.1 monocytes (b–e), and 3T3 cells (f–i) in 0 and 0.3 mg Fe/mL at day 1 (D1) (b,c,f,g) and day 4 (D4) (d,e,h,i) (n = 4).
Figure 6
Figure 6
Overlaid image (fluorescence and bright) of WEHI 274.1 monocytes cultured with (a) Cy5-MNPs or (b) Cy5-MCP-1-motif MNPs.
Figure 7
Figure 7
(a–h) Magnetic resonance images of mice injected with MCP-1-motif MNPs before and after experiments (wks = weeks); (i) Diagram of pixel density throughout the aorta area (n = 3) (* p < 0.05, compared to the same group of baseline).
Figure 8
Figure 8
(a–d) IVIS body fluorescence of ApoE KO mice, wild-type mice injected with Cy5-MCP-1-motif MNPs and Cy5-MNPs; (e) average radiant efficiency at 0 h of IVIS body fluorescence (n = 3) (* p < 0.05 compared with ApoE KO, MCP-1 NPs at the same injection time; ** p < 0.01 compared with ApoE KO, MCP-1 NPs at the same injection time).
Figure 9
Figure 9
IVIS organ fluorescence of ApoE KO mice injected with (a) PBS; (b) MCP-1-motif MNPs; (c) MNPs, and wild-type mice injected with (d) PBS; (e) MCP-1-motif MNPs; (f) MNPs. (g) Average radiant efficiency diagram of IVIS organ fluorescence (n = 3).
Figure 10
Figure 10
Prussian Blue and Oil Red O staining of the aorta of ApoE KO mice with injection of (a) PBS, (b)MNPs, and (c) MCP-1-motif MNPs (scale bar = 50 μm).
See this image and copyright information in PMC

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