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草药提取物高良姜素的天然产物纳米酶在肝细胞癌治疗中的应用

Natural product nanozymes of herbal extract galangin in managing hepatocellular carcinoma.

作者信息

Wang Erhao, Wu Yuxia, Wang Yan, Li Jiao, Liang Xiuzhen, Wang Zhongtao, Liu Xiaofei, Feng Faming, Mao JianCang, Zhu Yingqi, Li Le

机构信息

Hainan Women and Children's Medical Center, Haikou, China.

Hainan General Hospital/Hainan Affiliated Hospital of Hainan Medical University, Haikou, China.

出版信息

Front Chem. 2024 Jun 10;12:1426634. doi: 10.3389/fchem.2024.1426634. eCollection 2024.


DOI:10.3389/fchem.2024.1426634
PMID:38915904
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC11194749/
Abstract

Numerous local herbal extract species have been investigated as potential medicinal ingredients due to their promising anti-cancer properties. However, the primary constraint of the class of plant flavonoids lies in their low solubility and limited membrane permeability, leading to chemical instability and restricted bioavailability that impede biomedical applications. In this study, we have developed an ideal nanozyme-Galazyme, comprising galangin-loaded copper Nanozyme coated by DSPE-PEG, which amplifies oxidative stress to induce apoptosis via the regulation of reactive oxygen species (ROS) generation and mitogen-activated protein kinase (MAPK) activation. Galazyme exhibited significant peroxidase mimetic activity, demonstrating its potential to generate ROS and elevate oxidative stress. Upon uptake by HepG-2 cells, Galazyme efficiently converts excess hydrogen peroxide (H2O2) into highly reactive •OH radicals and upregulates MAPK expression, leading to the activation of Bax and Caspase 3, thereby promoting irreversible tumor cell apoptosis. Both and results demonstrate that Galazyme inhibits tumor cell growth and induces apoptosis by generating ample ROS and activating the MAPK pathway. Our study offers novel evidence supporting the enhancement of Galazyme-induced apoptosis through the upregulation of Bax and Caspase 3, along with the elucidation of the interaction between MAPK and apoptosis.

摘要

由于其具有潜在的抗癌特性,众多本地草药提取物物种已被作为潜在的药用成分进行研究。然而,植物类黄酮的主要限制在于其低溶解度和有限的膜通透性,导致化学不稳定性和生物利用度受限,从而阻碍了生物医学应用。在本研究中,我们开发了一种理想的纳米酶——Galazyme,它由负载高良姜素的铜纳米酶组成,并被DSPE-PEG包覆,通过调节活性氧(ROS)的产生和丝裂原活化蛋白激酶(MAPK)的激活来放大氧化应激以诱导细胞凋亡。Galazyme表现出显著的过氧化物酶模拟活性,证明了其产生活性氧和提高氧化应激的潜力。被HepG-2细胞摄取后,Galazyme能有效地将过量的过氧化氢(H2O2)转化为高活性的•OH自由基,并上调MAPK的表达,导致Bax和半胱天冬酶3的激活,从而促进不可逆的肿瘤细胞凋亡。 和 结果均表明,Galazyme通过产生活性氧和激活MAPK途径来抑制肿瘤细胞生长并诱导细胞凋亡。我们的研究提供了新的证据,支持通过上调Bax和半胱天冬酶3来增强Galazyme诱导的细胞凋亡,同时阐明了MAPK与细胞凋亡之间的相互作用。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/de89/11194749/d3ea371f4884/fchem-12-1426634-g004.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/de89/11194749/fc0f2ee3f233/FCHEM_fchem-2024-1426634_wc_sch1.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/de89/11194749/8aac9a7b5d8f/fchem-12-1426634-g001.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/de89/11194749/79d45e02939b/fchem-12-1426634-g002.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/de89/11194749/03dff2c3ea8e/fchem-12-1426634-g003.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/de89/11194749/d3ea371f4884/fchem-12-1426634-g004.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/de89/11194749/fc0f2ee3f233/FCHEM_fchem-2024-1426634_wc_sch1.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/de89/11194749/8aac9a7b5d8f/fchem-12-1426634-g001.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/de89/11194749/79d45e02939b/fchem-12-1426634-g002.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/de89/11194749/03dff2c3ea8e/fchem-12-1426634-g003.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/de89/11194749/d3ea371f4884/fchem-12-1426634-g004.jpg

相似文献

[1]
Natural product nanozymes of herbal extract galangin in managing hepatocellular carcinoma.

Front Chem. 2024-6-10

[2]
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[3]
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Free Radic Biol Med. 2014-2

[4]
Yellow Chaste Weed and Its Components, Apigenin and Galangin, Affect Proliferation and Oxidative Stress in Blue Light-Irradiated HaCaT Cells.

Nutrients. 2022-3-13

[5]
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Biomed Pharmacother. 2017-11-7

[6]
[Effects and mechanism of copper oxide nanozymes on wound healing of full-thickness skin defects in diabetic mice].

Zhonghua Shao Shang Za Zhi. 2020-12-20

[7]
Galangin potentiates human breast cancer to apoptosis induced by TRAIL through activating AMPK.

Biomed Pharmacother. 2017-5

[8]
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[9]
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J Mater Chem B. 2023-7-19

[10]
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引用本文的文献

[1]
Galangin-loaded chitosan nanoparticles inhibit the cell cycle progression and cell proliferation by modulating cyclin-dependent kinases in breast cancer cells.

Naunyn Schmiedebergs Arch Pharmacol. 2025-6-17

本文引用的文献

[1]
Carrier-Free Self-Assembly Nano-Sonosensitizers for Sonodynamic-Amplified Cuproptosis-Ferroptosis in Glioblastoma Therapy.

Adv Sci (Weinh). 2024-6

[2]
Nanozyme for tumor therapy: Surface modification matters.

Exploration (Beijing). 2021-9-1

[3]
Engineering Single-Atom Nanozymes for Catalytic Biomedical Applications.

Small. 2023-7

[4]
Iron-siRNA Nanohybrids for Enhanced Chemodynamic Therapy via Ferritin Heavy Chain Downregulation.

Angew Chem Int Ed Engl. 2023-5-22

[5]
Genetically Encoded Double-Stranded DNA-Based Nanostructure Folded by a Covalently Bivalent CRISPR/dCas System.

J Am Chem Soc. 2022-4-13

[6]
Oxygen Self-Supply Engineering-Ferritin for the Relief of Hypoxia in Tumors and the Enhancement of Photodynamic Therapy Efficacy.

Small. 2022-4

[7]
A Bioinspired Five-Coordinated Single-Atom Iron Nanozyme for Tumor Catalytic Therapy.

Adv Mater. 2022-4

[8]
Bright Bacterium for Hypoxia-Tolerant Photodynamic Therapy Against Orthotopic Colon Tumors by an Interventional Method.

Adv Sci (Weinh). 2021-8

[9]
Galangin Inhibits Gastric Cancer Growth Through Enhancing STAT3 Mediated ROS Production.

Front Pharmacol. 2021-4-26

[10]
Manganese-deposited iron oxide promotes tumor-responsive ferroptosis that synergizes the apoptosis of cisplatin.

Theranostics. 2021-3-13

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