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使用阳离子化直链淀粉纳米探针的肝癌增强荧光/磁共振双成像及基因治疗

Enhanced fluorescence/magnetic resonance dual imaging and gene therapy of liver cancer using cationized amylose nanoprobe.

作者信息

Zhang Hanchen, Deng Li, Liu Haiqing, Mai Siyao, Cheng Ziliang, Shi Guangzi, Zeng Hong, Wu Zhuo

机构信息

Department of Radiology, Sun Yat-Sen Memorial Hospital, Sun Yat-Sen University, Guangzhou, 510120, China.

Guangdong Provincial Key Laboratory of Malignant Tumor Epigenetics and Gene Regulation, Medical Research Center, Sun Yat-Sen Memorial Hospital, Sun Yat-Sen University, Guangzhou, 510120, China.

出版信息

Mater Today Bio. 2022 Feb 15;13:100220. doi: 10.1016/j.mtbio.2022.100220. eCollection 2022 Jan.

Abstract

Recently, various technologies for targeted gene release in cancer treatment have emerged. However, most of these strategies are facing the challenge of untraceable distribution and poor antitumour treatment effects. In this study, we constructed a gene delivery system that integrated a series of components to assemble multifunctional NPs, providing a promising theranostic nanoplatform for hepatocellular carcinoma (HCC) therapy. Cationized amylose (CA), superparamagnetic iron oxide (SPIO) nanoparticles (NPs), and tetraphenylethylene (TPE) were self-assembled to form nanospheres (CSP/TPE). The prepared NPs was modified with SP94 pepide through amidation reaction, and then survivin small interfering RNA (siRNA) were loaded into the NPs to form CSP/TPE@siRNA-SP94 NPs. Our results showed that the prepared NPs had good size distribution, high RNA condensation and transfection ability. CSP/TPE@siRNA-SP94 NPs exhibited excellent fluorescence and magnetic resonance (MR) imaging properties and . The prepared targeted NPs improved Huh-7 cellular uptake , and the biodistribution of CSP/TPE@siRNA-SP94 was observed through fluorescence imaging system and MRI. As survivin siRNA effectively retained in tumour cells, CSP/TPE@siRNA-SP94 NPs considerably inhibited tumour growth . In addition, H&E staining results showed that all the prepared CSP-based NPs had good biocompatibilities, as few histological changes or tumour metastasis were observed in major organs of the mice in the treatment group. Therefore, we envisage that the prepared CSP/TPE@siRNA-SP94 NPs can represent a promising strategy for HCC diagnosis and treatment.

摘要

近年来,癌症治疗中出现了各种靶向基因释放技术。然而,这些策略大多面临着分布难以追踪和抗肿瘤治疗效果不佳的挑战。在本研究中,我们构建了一种基因递送系统,该系统整合了一系列组件以组装多功能纳米粒子,为肝细胞癌(HCC)治疗提供了一个有前景的诊疗纳米平台。阳离子化直链淀粉(CA)、超顺磁性氧化铁(SPIO)纳米粒子(NPs)和四苯乙烯(TPE)自组装形成纳米球(CSP/TPE)。通过酰胺化反应将制备的纳米粒子用SP94肽修饰,然后将生存素小干扰RNA(siRNA)负载到纳米粒子中形成CSP/TPE@siRNA-SP94纳米粒子。我们的结果表明,制备的纳米粒子具有良好的尺寸分布、高RNA凝聚和转染能力。CSP/TPE@siRNA-SP94纳米粒子表现出优异的荧光和磁共振(MR)成像特性。制备的靶向纳米粒子提高了Huh-7细胞摄取,并通过荧光成像系统和MRI观察了CSP/TPE@siRNA-SP94的生物分布。由于生存素siRNA有效地保留在肿瘤细胞中,CSP/TPE@siRNA-SP94纳米粒子显著抑制了肿瘤生长。此外,苏木精-伊红(H&E)染色结果表明,所有制备的基于CSP的纳米粒子都具有良好的生物相容性,因为在治疗组小鼠的主要器官中几乎没有观察到组织学变化或肿瘤转移。因此,我们设想制备的CSP/TPE@siRNA-SP94纳米粒子可以代表一种有前景的HCC诊断和治疗策略。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/bf50/8861411/c72590358fbe/ga1.jpg

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