Liang Shuo, Ren Min, Chen Yanhong, Song Zhenchun, Yang Yapeng, Zhang Hong
Department of Radiology, Tianjin Chest Hospital, Tianjin 300022, China.
ACS Omega. 2025 Mar 17;10(11):10979-10986. doi: 10.1021/acsomega.4c09170. eCollection 2025 Mar 25.
This study aimed to evaluate iodinated nanoparticles based on Visipaque for the detection of macrophages in atherosclerotic plaques using computed tomography (CT). The nanoparticles were developed using Visipaque and hydrophobic groups to enhance the macrophages in atherosclerotic lesions. The nanoparticles were measured using NanoSight, and their cellular toxicity was evaluated using the cell counting kit-8 assay. RAW264.7 macrophages were used to detect the cellular uptake of the nanoparticles. Aortic atherosclerotic plaques were induced in New Zealand rabbits ( = 6) by combining a high-cholesterol diet and aortic injury. The noninjured rabbits ( = 4) were fed a normal chow diet and used as controls. CT scans before and 2 h after Visipaque injection, followed by nanoparticle imaging 1 h later. Macrophages were counted using immunohistology with an anti-CD68 monoclonal antibody. The diameter of the nanoparticle agent was approximately 150 mM, and 90% varied broadly between 69 and 248 nm. In vitro experiments demonstrated that the nanoparticles had low cellular toxicity and were effectively endocytosed by macrophages in a time- and dose-dependent manner. In vivo, CT imaging demonstrated that the nanoparticle density was higher in the aortic wall plaques in atherosclerotic rabbits than in control rabbits. The histologic staining confirmed successful atherosclerosis modeling in rabbits and abundant macrophage infiltration in the aortic wall, preferentially taking up the nanoparticles. In conclusion, this study suggests that the novel nanoparticles could be a promising, effective contrast agent for the detection of macrophages in atherosclerotic plaques using CT.
本研究旨在评估基于威视派克的碘化纳米颗粒，用于通过计算机断层扫描（CT）检测动脉粥样硬化斑块中的巨噬细胞。这些纳米颗粒是利用威视派克和疏水基团开发的，以增强动脉粥样硬化病变中的巨噬细胞。使用纳米可视粒度分析仪测量纳米颗粒，并使用细胞计数试剂盒-8检测法评估其细胞毒性。采用RAW264.7巨噬细胞检测纳米颗粒的细胞摄取情况。通过高胆固醇饮食和主动脉损伤相结合的方法，在6只新西兰兔中诱导主动脉粥样硬化斑块形成。将4只未受伤的兔子喂食正常饲料作为对照。在注射威视派克前及注射后2小时进行CT扫描，1小时后进行纳米颗粒成像。使用抗CD68单克隆抗体通过免疫组织学方法计数巨噬细胞。纳米颗粒制剂的直径约为150 mM，90%的颗粒直径在69至248 nm之间广泛变化。体外实验表明，纳米颗粒具有低细胞毒性，并能以时间和剂量依赖性方式被巨噬细胞有效内吞。在体内，CT成像显示，动脉粥样硬化兔主动脉壁斑块中的纳米颗粒密度高于对照兔。组织学染色证实兔动脉粥样硬化模型构建成功，主动脉壁有大量巨噬细胞浸润，并优先摄取纳米颗粒。总之，本研究表明，这种新型纳米颗粒可能是一种有前景的、有效的造影剂，用于通过CT检测动脉粥样硬化斑块中的巨噬细胞。
