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基于锰锌铁氧体纳米粒子的新型肝细胞癌检测磁共振成像纳米探针:体外和体内评估。

Novel MR imaging nanoprobe for hepatocellular carcinoma detection based on manganese-zinc ferrite nanoparticles: in vitro and in vivo assessments.

机构信息

Department of Medical Physics, School of Medicine, Isfahan University of Medical Sciences, Isfahan, Iran.

Department of Materials Engineering, Isfahan University of Technology, Isfahan, Iran.

出版信息

J Cancer Res Clin Oncol. 2023 Jul;149(8):4939-4957. doi: 10.1007/s00432-022-04427-x. Epub 2022 Oct 29.

Abstract

PURPOSE

Achieving new contrast enhancer agents that can produce high-resolution images in magnetic resonance imaging (MRI) with a minimum dose and side effects has always been important.

METHODS

Herein, the pegylated curcumin-coated manganese-zinc ferrite nanoparticles (MZF@CA-PEG-CUR NPs) have been reported as an MR imaging nanoprobe in hepatocellular carcinoma detection in the murine model for the first time. In vitro studies were done on HEPA 1-6 cancer cells and L929 as normal cells, and in vivo studies were done on hepatocellular carcinoma (HCC) using xenograft models of HCC.

RESULTS

The prepared NP had a diameter of 105 nm with narrow size distribution and was superparamagnetic with a saturated magnetization (Ms) of 39 emu/g. The NP was biocompatible without any significant hemolysis and cytotoxicity. Prussian blue staining showed more cellular uptake of HEPA 1-6 compared to L929 control cells after incubation (P < 0.05). The concentration of Fe in mice blood confirmed the plasma half-life of about 3 h; it seems the PEGylation increased the circulation time. ICP-OES of Fe showed the highest tumor localization for MZF@CA-CUR-PEG NPs, due to passive accumulation, compared to the other mice studied organs. The r relaxivity of NPs was 134.89 mM s, and in vitro MRI demonstrated better effects in HEPA 1-6 cells than in L929 (P < 0.05). Also, in vivo MR images showed signal enhancement efficacy in tumor-bearing mice.

CONCLUSION

This study demonstrated that the MZF@CA-CUR-PEG nanoprobe could be a promising candidate as an MR imaging agent in hepatocellular carcinoma early detection.

摘要

目的

始终以来,寻求可在磁共振成像(MRI)中产生高分辨率图像且剂量和副作用最小的新型对比增强剂一直很重要。

方法

本研究首次报道了聚乙二醇化姜黄素包覆的锰锌铁氧体纳米粒子(MZF@CA-PEG-CUR NPs)作为肝癌检测的 MRI 纳米探针。在体外研究中,我们在 HEPA 1-6 癌细胞和 L929 正常细胞上进行了研究,在肝癌(HCC)的异种移植模型中进行了体内研究。

结果

所制备的 NP 粒径为 105nm,粒径分布较窄,具有超顺磁性,饱和磁化强度(Ms)为 39 emu/g。NP 具有良好的生物相容性,无明显溶血和细胞毒性。普鲁士蓝染色显示,与 L929 对照细胞相比,孵育后 HEPA 1-6 细胞摄取 NP 更多(P<0.05)。小鼠血液中 Fe 的浓度证实了其血浆半衰期约为 3 h;PEG 化似乎增加了循环时间。ICP-OES 显示,由于被动积累,与其他研究的小鼠器官相比,MZF@CA-CUR-PEG NPs 在肿瘤中的定位最高。NP 的 r2 弛豫率为 134.89 mM s,体外 MRI 显示其对 HEPA 1-6 细胞的效果优于 L929(P<0.05)。此外,体内 MRI 图像显示荷瘤小鼠的信号增强效果。

结论

本研究表明,MZF@CA-CUR-PEG 纳米探针有望成为肝癌早期检测的 MRI 造影剂的候选物。

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