用铁修饰并包覆癌细胞膜的介孔多多巴胺纳米粒子治疗小鼠器官的毒性和氧化应激生物标志物

IF 6.6 2区 医学 Q1 NANOSCIENCE & NANOTECHNOLOGY
International Journal of Nanomedicine Pub Date : 2024-11-19 eCollection Date: 2024-01-01 DOI:10.2147/IJN.S481120
Marta Szukalska, Bartosz F Grześkowiak, Magdalena J Bigaj-Józefowska, Marta Witkowska, Emilia Cicha, Patrycja Sujka-Kordowska, Izabela Miechowicz, Michał Nowicki, Radosław Mrówczyński, Ewa Florek
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引用次数: 0

摘要

目的:聚多巴胺纳米粒子(PDA NPs)在医学领域具有巨大潜力。它们在癌症治疗、成像、化疗、光动力疗法(PDT)、光热疗法(PTT)和组织修复方面的应用正受到广泛研究。我们的研究旨在评估用介孔 PDA NPs(MPDAFe NPs)处理过的动物器官的体内毒性和氧化应激生物标志物的变化:从 BALB/c 裸鼠肝脏和肾脏匀浆中提取异种移植的 HepG2 人肝癌细胞,用铁修饰的介孔 PDA 纳米粒子(MPDAFe@DOX@Mem NPs)处理,包覆癌细胞膜并负载多柔比星(DOX),然后进行 PTT。这些样本用于组织学评估和氧化应激生物标志物的测量,包括总蛋白(TP)、还原型谷胱甘肽(GSH)、一氧化氮(NO)、S-亚硝基硫醇(RSNO)、硫代巴比妥酸活性物质(TBARS)、三氧化碳当量抗氧化能力(TEAC)、过氧化氢酶(CAT)、谷胱甘肽S-转移酶(GST)和超氧化物歧化酶(SOD):在肾脏中,与对照组相比,MPDAFe@DOX@Mem NPs 与 PTT 联用可提高 GSH(43%)、TBARS(32%)和 CAT(27%),而 SOD 则降低了 20%。此外,肝脏中的 CAT 活性增加了 79%:结论:使用 MPDAFe@DOX@Mem NPs 和 PTT 后,肾脏中的氧化应激参数和组织学变化存在显著差异,肾脏的变化比肝脏更明显,表明肾脏存在潜在毒性。我们的研究为介孔 PDA NPs 与化疗-光热疗法(CT-PTT)联合体内给药后的氧化应激和可能的毒性效应提供了见解,这对它们未来在抗癌疗法中的应用极为重要。
本文章由计算机程序翻译,如有差异,请以英文原文为准。
Toxicity and Oxidative Stress Biomarkers in the Organs of Mice Treated with Mesoporous Polydopamine Nanoparticles Modified with Iron and Coated with Cancer Cell Membrane.

Purpose: Polydopamine nanoparticles (PDA NPs) have great potential in medicine. Their applications being widely investigated in cancer therapy, imaging, chemotherapy, photodynamic therapy (PDT), photothermal therapy (PTT), and tissue repair. The aim of our study was to assess the in vivo toxicity and changes in oxidative stress biomarkers in organs of animals treated with mesoporous PDA NPs modified with iron (MPDAFe NPs), coated with the cancer cell membrane and loaded with doxorubicin (DOX), and subsequently subjected to PTT.

Methods: Liver and kidney homogenates were obtained from BALB/c nude mice with xenograft HepG2 human hepatoma cells, treated with iron modified mesoporous PDA nanoparticles, coated with the cancer cell membrane and loaded with doxorubicin (MPDAFe@DOX@Mem NPs), and subjected to PTT. These samples were used for histological evaluation and measurement of oxidative stress biomarkers, including total protein (TP), reduced glutathione (GSH), nitric oxide (NO), S-nitrosothiols (RSNO), thiobarbituric acid reactive substances (TBARS), trolox equivalent antioxidant capacity (TEAC), catalase (CAT), glutathione S-transferase (GST), and superoxide dismutase (SOD).

Results: In the kidney, MPDAFe@DOX@Mem NPs in combination with PTT increased GSH (43%), TBARS (32%), and CAT (27%), while SOD decreased by 20% compared to the control group. Additionally, CAT activity in the liver increased by 79%.

Conclusion: Significant differences in oxidative stress parameters and histological changes after administration with MPDAFe@DOX@Mem NPs and PTT were observed in the kidneys, showing more pronounced changes than the liver, indicating potential kidney toxicity. Our research provides insights into oxidative stress and possible toxic effects after in vivo administration of mesoporous PDA NPs combined with chemotherapy-photothermal therapy (CT-PTT), which is extremely important for their future applications in anticancer therapies.

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来源期刊
International Journal of Nanomedicine
International Journal of Nanomedicine NANOSCIENCE & NANOTECHNOLOGY-PHARMACOLOGY & PHARMACY
CiteScore
14.40
自引率
3.80%
发文量
511
审稿时长
1.4 months
期刊介绍: The International Journal of Nanomedicine is a globally recognized journal that focuses on the applications of nanotechnology in the biomedical field. It is a peer-reviewed and open-access publication that covers diverse aspects of this rapidly evolving research area. With its strong emphasis on the clinical potential of nanoparticles in disease diagnostics, prevention, and treatment, the journal aims to showcase cutting-edge research and development in the field. Starting from now, the International Journal of Nanomedicine will not accept meta-analyses for publication.
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