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In vivo MRI detection of intraplaque macrophages with biocompatible silica-coated iron oxide nanoparticles in murine atherosclerosis
Journal of Applied Biomaterials & Functional Materials ( IF 2.5 ) Pub Date : 2021-09-14 , DOI: 10.1177/22808000211014751
Chan Woo Kim 1, 2 , Byung-Hee Hwang 1, 2 , Hyeyoung Moon 3 , Jongeun Kang 3, 4 , Eun-Hye Park 1, 2 , Sang-Hyun Ihm 1, 5 , Kiyuk Chang 1, 2 , Kwan Soo Hong 3, 4
Affiliation  

Identification of a vulnerable atherosclerotic plaque before rupture is an unmet clinical need. Integrating nanomedicine with multimodal imaging has the potential to precisely detect biological processes in atherosclerosis. We synthesized silica-coated iron oxide nanoparticles (SIONs) coated with rhodamine B isothiocyanate and polyethylene glycol and investigated their feasibility in the detection of macrophages in inflamed atherosclerotic plaques of apolipoprotein E-deficient (ApoE−/−) mice via magnetic resonance (MR) and fluorescence reflectance (FR) imaging. In vitro cellular uptake of SIONs was assessed in macrophages using confocal laser scanning microscopy (CLSM). In vivo MR imaging was performed 24 h after SION injection via the tail vein in 26-week-old ApoE−/− mice fed a high-cholesterol diet (HCD). We also performed FR imaging of the extracted aortas from four different mice: two normal-diet-fed C57BL/6 mice injected with saline or 10 mg/kg SIONs and two HCD-fed ApoE−/− mice injected with 5 or 10 mg/kg SIONs. The harvested aortas were cryosectioned and stained with immunohistochemical staining. The CLSM images at 24 h after incubation showed efficient uptake of SIONs by macrophages, with no evidence of cytotoxicity. The in vivo and ex vivo MR and FR images demonstrated SION deposition in the atheroma. Upon immunohistochemical staining of the aorta, CLSM images revealed colocalization of macrophages and SIONs in the atherosclerotic plaque. These results demonstrate that polyethylene glycosylated SIONs could be a highly effective method to identify macrophage activity in atherosclerotic plaques as a multimodal imaging agent.



中文翻译:

小鼠动脉粥样硬化中具有生物相容性二氧化硅包覆氧化铁纳米颗粒的斑块内巨噬细胞的体内 MRI 检测

在破裂前识别易损的动脉粥样硬化斑块是未满足的临床需求。将纳米医学与多模态成像相结合有可能精确检测动脉粥样硬化的生物过程。我们合成了涂有罗丹明 B 异硫氰酸酯和聚乙二醇的二氧化硅涂层氧化铁纳米粒子 (SION),并研究了它们在通过磁共振 (MR)检测载脂蛋白 E 缺陷 (ApoE -/- ) 小鼠发炎动脉粥样硬化斑块中巨噬细胞的可行性和荧光反射 (FR) 成像。使用共聚焦激光扫描显微镜 (CLSM) 在巨噬细胞中评估 SION 的体外细胞摄取。在 26 周龄的 ApoE -/- 中通过尾静脉注射 SION 后 24 小时进行体内 MR 成像喂食高胆固醇饮食(HCD)的小鼠。我们还对来自四只不同小鼠的提取主动脉进行了 FR 成像:两只正常饮食喂养的 C57BL/6 小鼠注射了生理盐水或 10 mg/kg SION 和两只 HCD 喂养的 ApoE -/-注射 5 或 10 mg/kg SION 的小鼠。收获的主动脉被冷冻切片并用免疫组织化学染色进行染色。孵育后 24 小时的 CLSM 图像显示巨噬细胞有效吸收 SION,没有细胞毒性的证据。体内和体外 MR 和 FR 图像证明了 SION 在粥样斑块中的沉积。对主动脉进行免疫组织化学染色后,CLSM 图像显示巨噬细胞和 SION 在动脉粥样硬化斑块中的共定位。这些结果表明,聚乙二醇化的 SIONs 可以作为一种多模式成像剂来鉴定动脉粥样硬化斑块中的巨噬细胞活性。

更新日期:2021-09-15
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