Fe3O4-viral-like Mesoporous Silica Nanoparticle(Fe3O4-vMSN)-Sustained Release of Lenvatinib for Targeted Treatment of Hepatocellular Carcinoma.

IF 2.3 4区医学 Q3 ONCOLOGY

Current cancer drug targets Pub Date : 2025-01-14 DOI:10.2174/0115680096329105241031093859

Xue Wang, Tianzhao Xu, Hui Song, Lanmei Zhou, Xinyi Li, Guangli Li, Xinghui Liu

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引用次数: 0

Abstract

Background: Lenvatinib is an oral tyrosine kinase inhibitor that selectively inhib-its receptors involved in tumor angiogenesis and tumor growth. It is an emerging first-line treatment agent for hepatocellular carcinoma (HCC). However, there is no intravenous ad-ministration of Lenvatinib.

Aims: This study aimed to construct nanocomposites that can efficiently support Lenvatinib and target liver cancer tissues and cells.

Objective: In this study, ferric oxide-viral-like mesoporous silica nanoparticles-folic acid (Fe3O4-vMSN-FA) nanocomposites loaded with Lenvatinib were constructed, and their anti-hepatocellular carcinoma effects were evaluated.

Methods: The hydrothermal method was used to synthesize ferric oxide (Fe3O4). Ferric ox-ide-viral-like mesoporous silica nanoparticles (Fe3O4-vMSN) were synthesized using a two-phase method. Then, Fe3O4-vMSN was modified with folic acid (Fe3O4-vMSN-FA) to better target tumor cells.

Results: The experimental data showed that Fe3O4-vMSN-FA nanocomposites were suc-cessfully synthesized and could be loaded with Lenvatinib (Len@ Fe3O4-vMSN-FA). Fe3O4-vMSN-FA had good stability and biocompatibility, and it can release the loaded Len-vatinib faster in an acidic environment (pH 5.5). CCK8 assay and flow cytometry showed that HepG2 cells in the Len@ Fe3O4-vMSN group had the lowest cell viability and the high-est apoptosis rate, confirming the anticancer properties of Len@ Fe3O4-vMSN-FA in vitro. In addition, transwell experiments showed that the migration and invasion ability of HepG2 cells in the Len@ Fe3O4-vMSN-FA group were significantly inhibited. In vivo fluorescence imaging in mice confirmed the enhanced tumor-targeting ability of Fe3O4-vMSN-FA. The tumor volume of the Len@ Fe3O4-vMSN-FA group was significantly reduced, and there was no significant effect on body weight. Moreover, serum liver function index (ALT and AST) and HE staining showed that Len@ Fe3O4-vMSN-FA did not cause obvious damage to organ tissue.

Conclusion: Len@ Fe3O4-vMSN-FA has a good anti-liver cancer effect. Fe3O4-vMSN-FA can be used as an alternative platform for MSCs for drug delivery, providing more options for cancer therapy.

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fe3o4 -病毒样介孔二氧化硅纳米颗粒（Fe3O4-vMSN）缓释Lenvatinib靶向治疗肝细胞癌

背景：Lenvatinib是一种口服酪氨酸激酶抑制剂，选择性抑制参与肿瘤血管生成和肿瘤生长的受体。它是一种新兴的治疗肝细胞癌（HCC）的一线药物。然而，没有静脉给药Lenvatinib。目的：构建高效支持Lenvatinib靶向肝癌组织和细胞的纳米复合材料。目的：构建载Lenvatinib的氧化铁-病毒样介孔二氧化硅纳米颗粒-叶酸（Fe3O4-vMSN-FA）纳米复合材料，并评价其抗肝癌作用。方法：采用水热法合成氧化铁（Fe3O4）。采用两相法合成了氧化铁病毒样介孔二氧化硅纳米颗粒（Fe3O4-vMSN）。然后用叶酸修饰Fe3O4-vMSN (Fe3O4-vMSN- fa)，使其更好地靶向肿瘤细胞。结果：实验数据表明，成功合成了Fe3O4-vMSN-FA纳米复合材料，并可负载Lenvatinib （Len@ Fe3O4-vMSN-FA）。Fe3O4-vMSN-FA具有良好的稳定性和生物相容性，在酸性环境（pH 5.5）下可较快地释放负载的Len-vatinib。CCK8实验和流式细胞术显示，Len@ Fe3O4-vMSN组HepG2细胞的细胞活力最低，凋亡率最高，证实了Len@ Fe3O4-vMSN- fa的体外抗癌作用。此外，transwell实验显示，Len@ Fe3O4-vMSN-FA组HepG2细胞的迁移和侵袭能力明显受到抑制。小鼠体内荧光成像证实了Fe3O4-vMSN-FA增强的肿瘤靶向能力。Len@ Fe3O4-vMSN-FA组肿瘤体积明显减小，对体重无显著影响。血清肝功能指数（ALT、AST）及HE染色显示Len@ Fe3O4-vMSN-FA对脏器组织无明显损伤。结论：Len@ Fe3O4-vMSN-FA具有良好的抗肝癌作用。Fe3O4-vMSN-FA可作为MSCs给药的替代平台，为癌症治疗提供更多选择。

本文章由计算机程序翻译，如有差异，请以英文原文为准。

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来源期刊

Current cancer drug targets 医学-肿瘤学

CiteScore

5.40

自引率

0.00%

发文量

105

审稿时长

1 months

期刊介绍： Current Cancer Drug Targets aims to cover all the latest and outstanding developments on the medicinal chemistry, pharmacology, molecular biology, genomics and biochemistry of contemporary molecular drug targets involved in cancer, e.g. disease specific proteins, receptors, enzymes and genes. Current Cancer Drug Targets publishes original research articles, letters, reviews / mini-reviews, drug clinical trial studies and guest edited thematic issues written by leaders in the field covering a range of current topics on drug targets involved in cancer. As the discovery, identification, characterization and validation of novel human drug targets for anti-cancer drug discovery continues to grow; this journal has become essential reading for all pharmaceutical scientists involved in drug discovery and development.