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唾液酸修饰的介孔聚多巴胺双重负载转铁蛋白基因和超顺磁性氧化铁用于实现 HCC 的内源性和外源性协同 T2 加权磁共振成像。

Sialic acid-engineered mesoporous polydopamine dual loaded with ferritin gene and SPIO for achieving endogenous and exogenous synergistic T2-weighted magnetic resonance imaging of HCC.

机构信息

Department of Radiology, Key Laboratory of Imaging Diagnosis and Minimally Invasive Intervention Research, School of Medicine, Lishui Hospital of Zhejiang University, Lishui, 323000, Zhejiang, China.

Department of Radiology, Sir Run Shaw Affiliated Hospital, School of Medicine, Zhejiang University, Hangzhou, 310058, China.

出版信息

J Nanobiotechnology. 2021 Mar 17;19(1):76. doi: 10.1186/s12951-021-00821-8.

Abstract

BACKGROUND

Hepatocellular carcinoma (HCC) is a common malignant tumor with poor prognosis. Magnetic resonance imaging (MRI) is one of the most effective imaging methods for the early diagnosis of HCC. However, the current MR contrast agents are still facing challenges in the early diagnosis of HCC due to their relatively low sensitivity and biosafety. Thus, the development of effective MR agents is highly needed for the early diagnosis of HCC.

RESULTS

Herein, we fabricated an HCC-targeted nanocomplexes containing SPIO-loaded mesoporous polydopamine (MPDA@SPIO), sialic acid (SA)-modified polyethyleneimine (SA-PEI), and alpha-fetoprotein regulated ferritin gene (AFP-Fth) which was developed for the early diagnosis of HCC. It was found that the prepared nanocomplexes (MPDA@SPIO/SA-PEI/AFP-Fth) has an excellent biocompatibility towards the liver cells. In vivo and in vivo studies revealed that the transfection of AFP-Fth gene in hepatic cells significantly upregulated the expression level of ferritin, thereby resulting in an enhanced contrast on T2-weighted images via the formed endogenous MR contrast.

CONCLUSIONS

The results suggested that MPDA@SPIO/SA-PEI/AFP-Fth had a superior ability to enhance the MR contrast of T2-weighted images of tumor region than the other preparations, which was due to its HCC-targeted ability and the combined T2 contrast effect of endogenous ferritin and exogenous SPIO. Our study proved that MPDA@SPIO/SA-PEI/AFP-Fth nanocomplexes could be used as an effective MR contrast agent to detect HCC in the early stage.

摘要

背景

肝细胞癌(HCC)是一种预后较差的常见恶性肿瘤。磁共振成像(MRI)是 HCC 早期诊断最有效的影像学方法之一。然而,由于目前的 MR 对比剂的灵敏度和生物安全性相对较低,其在 HCC 的早期诊断中仍面临挑战。因此,开发有效的 MR 造影剂对于 HCC 的早期诊断非常重要。

结果

本研究制备了一种包含负载超顺磁性氧化铁(SPIO)的介孔聚多巴胺(MPDA@SPIO)、唾液酸(SA)修饰的聚乙烯亚胺(SA-PEI)和甲胎蛋白调控的铁蛋白基因(AFP-Fth)的 HCC 靶向纳米复合物,用于 HCC 的早期诊断。结果表明,所制备的纳米复合物(MPDA@SPIO/SA-PEI/AFP-Fth)对肝细胞具有良好的生物相容性。体内和体内研究表明,AFP-Fth 基因在肝细胞中的转染显著上调了铁蛋白的表达水平,从而通过形成内源性 MR 对比增强 T2 加权图像的对比。

结论

结果表明,与其他制剂相比,MPDA@SPIO/SA-PEI/AFP-Fth 具有增强肿瘤区域 T2 加权图像 MR 对比的优异能力,这是由于其 HCC 靶向能力以及内源性铁蛋白和外源性 SPIO 的联合 T2 对比效应。我们的研究证明,MPDA@SPIO/SA-PEI/AFP-Fth 纳米复合物可用作检测 HCC 的有效 MR 造影剂。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/9989/7968241/6b911186a36f/12951_2021_821_Fig1_HTML.jpg

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