Division of Nephrology, Peking University Third Hospital, Beijing, 100191, People's Republic of China.
Institute of Basic Medical Sciences Chinese Academy of Medical Sciences, School of Basic Medicine Peking Union Medical College, Beijing, 100005, People's Republic of China.
Int J Nanomedicine. 2021 Mar 18;16:2271-2282. doi: 10.2147/IJN.S299004. eCollection 2021.
Contrast-enhanced magnetic resonance imaging (MRI) is a powerful diagnostic tool for many diseases. In many situations, the contrasts are repeatedly administrated in order to monitor and assess the disease progression.
To investigate and compare the biological effects of γ-FeO nanoparticle (NP) and gadolinium dimeglumine (Gd-DTPA) with high and multiple doses on the kidney of healthy mice.
Polydextrose sorbitol carboxymethyl ether coated γ-FeO NP with hydrodynamic size of 68.2 nm and clinically applied Gd-DTPA were employed on healthy mice with the repeatedly intravenous administration of high doses. The cell viability of human umbilical vein endothelial cells (HUVEC) in high doses of these two contrast agents were measured using the xCELLigence Real-Time Cell Analysis (RTCA) S16 Instrument. The biological effects of γ-FeO NP and Gd-DTPA on the kidney were obtained using a biochemical automatic analyzer and multiple proinflammatory factor kit on the serum. Histopathological and immunohistochemistry analysis were taken on kidney tissues.
It showed that the proinflammatory responses elicited by the γ-FeO NPs were weaker than that by Gd-DTPA, evidenced by the relatively much lower level of IL-1β, IL-6, IL-18, TNF-α, C-reactive protein (CRP) and Ferritin. At the same time, the γ-FeO NPs did not have the biochemical index elevated, while the Gd-DTPA did.
The γ-FeO NPs induced weaker proinflammatory effects in reference to the Gd-DTPA, indicating better renal safety. Therefore, it is suggested that γ-FeO NPs should be safer and optional choice when repeated contrast-enhanced MRI is necessary.
对比增强磁共振成像(MRI)是许多疾病的强大诊断工具。在许多情况下,为了监测和评估疾病进展,会反复给药对比剂。
研究和比较高剂量和多次给药的γ-FeO 纳米颗粒(NP)和钆二葡甲胺(Gd-DTPA)对健康小鼠肾脏的生物学效应。
使用临床应用的 Gd-DTPA 和具有 68.2nm 水动力粒径的聚右旋糖酐山梨醇羧甲基醚包裹的γ-FeO NP,对健康小鼠进行高剂量重复静脉给药。使用 xCELLigence 实时细胞分析(RTCA)S16 仪器测量这两种造影剂高剂量下的人脐静脉内皮细胞(HUVEC)的细胞活力。使用生化自动分析仪和多种促炎因子试剂盒检测γ-FeO NP 和 Gd-DTPA 对血清中肾脏的生物学效应。对肾组织进行组织病理学和免疫组织化学分析。
结果表明,γ-FeO NPs 引起的炎症反应比 Gd-DTPA 弱,这表现在较低水平的白细胞介素-1β(IL-1β)、白细胞介素-6(IL-6)、白细胞介素-18(IL-18)、肿瘤坏死因子-α(TNF-α)、C 反应蛋白(CRP)和铁蛋白。同时,γ-FeO NPs 没有升高生化指标,而 Gd-DTPA 则有。
γ-FeO NPs 引起的促炎作用比 Gd-DTPA 弱,表明肾脏安全性更好。因此,当需要重复对比增强 MRI 时,建议选择γ-FeO NPs 作为更安全的选择。