Original ArticleMagnetic mesoporous silica nanoparticles-aided dual MR/NIRF imaging to identify macrophage enrichment in atherosclerotic plaques
Graphical Abstract
Herein, a novel magnetic mesoporous silica nanoparticle loaded with IR820 (PP1-IO@MS-IR820, PIMI) was fabricated to specifically target and quantify macrophage enrichment in atherosclerotic plaque. As illustrated in graphical abstract figure, by conjugating PP1, an overexpressed surface receptor (SR-AI) driven foamy macrophage-targeted peptide, PIMI was designed for conducing efficiently plaque-targeted imaging. Specifically, IO was used as a magnetic core for T2 and T2*-weighted MR imaging; a mesoporous silica layer was prepared to load NIRF dye (IR820) for optical imaging; and the two imaging elements were superimposed to finally achieve dual-mode imaging effect. As a result, the obtained PIMI exhibited improved foamy macrophage deposition and favored atherosclerotic plaque imaging in MR/NIRF dual-modal, which was confirmed by staining of tissue sections.
Section snippets
Synthesis of IO magnetic nanoparticles
1.4 g (4 mmol) of the Fe(acac)3 was dissolved in 40 mL of dibenzyl ether, followed by addition of oleic acid (4 mL, 12 mmol) and oleylamine (12 mL, 36 mmol) at room temperature. The mixture was heated to 220 °C for 1 h and was heated to 290 °C for 30 min. At room temperature, 80 ml of ethanol was added to the solution, and the IO nanoparticles were precipitated and dispersed in chloroform.
Synthesis of IO@MS nanoparticles
1 g cetyltrimethyl ammonium bromide (CTAB) and 0.01 g triethanolamine (TEA) were dissolved in 20 mL of
Synthesis and characterization of PIMI
This nanoparticle was successfully synthesized by several steps. Firstly, IO was obtained according to the high temperature thermal decomposition approach. To provide loading sites and better biocompatibility for in vivo application, mesoporous silica (MS) was deposited on IO. Then PP1 peptide was subsequently conjugated via the amide condensation reaction, and IR820 was loaded to form the PIMI nanoparticle. TEM images showed the core/shell structure of PIMI nanoparticles with approximately
Discussion
Foamy macrophage plays a key role in atherosclerotic plaque formation, progression and destabilization.31, 32, 33 High content of foamy macrophages in plaque indicates severe inflammation activity, which provides a compelling measurable marker for modern imaging techniques. Clinical imaging approaches, such as CTA and MRA, usually evaluate plaque size based on the degree of luminal stenosis. However, these methods cannot fully picture such active biological components related to high-risk
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Conflict of interest: The authors declare no competing financial interests.
Funding: This work was supported by the Natural Science Foundation of China (81701826, 81971673), Tianjin Science and Technology Project (19KPHDRC00100), Key Program of the Tianjin Health and Family Planning Commission (16KG115), the Youth Science Foundation of the Second Hospital Center Laboratory of Tianjin Medical University (2018ydey11), and Science Foundation of Tianjin Medical University (2019KJ165).
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These authors contributed equally to this work.
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Mailing address: No. 23, Pingjiang Road, Hexi District, Tianjin 300211, P.R. China.