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多糖修饰的硒纳米颗粒对荷H22肿瘤小鼠的免疫调节作用

Immunoregulatory Effects of Polysaccharide Modified Selenium Nanoparticles on H22 Tumor-Bearing Mice.

作者信息

Long Yan, Ji Hongfei, Yang Jiajing, Ji Haiyu, Dai Keyao, Ding Wenjie, Zheng Guoqiang, Yu Juan

机构信息

Yantai Key Laboratory of Characteristic Agricultural Bioresource Conservation & Germplasm Innovative Utilization, School of Life Sciences, Yantai University, Yantai 264005, China.

College of Food Science and Engineering, Tianjin University of Science and Technology, Tianjin 300457, China.

出版信息

Foods. 2024 Dec 17;13(24):4073. doi: 10.3390/foods13244073.

Abstract

polysaccharide (CPP) and rare element selenium (Se) have been proved to exert various biological activities, and our previous study demonstrated that selenium nanoparticles modified with CPP (CPP-SeNPs) possessed significantly enhanced tumor cytotoxicity in vitro. This study aimed to investigated the inhibitory effects of CPP-SeNPs complex on H22 solid tumors via immune enhancement. In this study, the H22 tumor-bearing mice model was constructed, and the potential mechanisms of CPP-SeNPs antitumor effects were further explored by evaluating cytokines expression levels, immune cells activities and tumor cells apoptotic indicators in each group. The results demonstrated that CPP-SeNPs effectively exerted dose-dependent protective effects on the immune organs of tumor-bearing mice in vivo, leading to increase in peripheral white blood cell counts and inhibition of solid tumor growth with inhibitory rate of 47.18% in high-dose group (1.5 mg/kg). Furthermore, CPP-SeNPs treatment significantly elevated the levels of TNF-α, IFN-γ, and IL-2 in mice sera, enhanced NK cell cytotoxicity, augmented macrophage phagocytosis capacity, as well as increased both the amounts and proliferation activity of lymphocyte subsets. CPP-SeNPs improved the immune system's ability to clear tumor cells by up-regulating Bax expression while down-regulating Bcl-2 expression within solid tumors, indicating the potential activation of mitochondrial apoptosis pathway. Therefore, CPP-SeNPs administration can effectively inhibit tumor growth by enhancing immune response in tumor-bearing mice, which might be relevant to the regulation of gut microbiota short-chain fatty acids metabolisms. These findings could provide theoretical support and data foundation for further development of CPP-SeNPs as functional food and drug adjuvants.

摘要

多糖(CPP)和稀有元素硒(Se)已被证明具有多种生物活性,我们之前的研究表明,用CPP修饰的硒纳米颗粒(CPP-SeNPs)在体外具有显著增强的肿瘤细胞毒性。本研究旨在通过免疫增强作用研究CPP-SeNPs复合物对H22实体瘤的抑制作用。在本研究中,构建了荷H22肿瘤小鼠模型,并通过评估每组细胞因子表达水平、免疫细胞活性和肿瘤细胞凋亡指标,进一步探讨CPP-SeNPs抗肿瘤作用的潜在机制。结果表明,CPP-SeNPs在体内对荷瘤小鼠的免疫器官有效发挥剂量依赖性保护作用,导致外周白细胞计数增加,抑制实体瘤生长,高剂量组(1.5 mg/kg)的抑制率为47.18%。此外,CPP-SeNPs处理显著提高了小鼠血清中TNF-α、IFN-γ和IL-2的水平,增强了NK细胞的细胞毒性,增强了巨噬细胞的吞噬能力,以及增加了淋巴细胞亚群的数量和增殖活性。CPP-SeNPs通过上调实体瘤内Bax表达同时下调Bcl-2表达,提高了免疫系统清除肿瘤细胞的能力,表明线粒体凋亡途径可能被激活。因此,给予CPP-SeNPs可以通过增强荷瘤小鼠的免疫反应有效抑制肿瘤生长,这可能与肠道微生物群短链脂肪酸代谢的调节有关。这些发现可为CPP-SeNPs作为功能性食品和药物佐剂的进一步开发提供理论支持和数据基础。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/46ee/11675135/abb401ebf1df/foods-13-04073-g001.jpg

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