功能化磁珠NK细胞对宫颈癌小鼠作用的研究。

IF 4.7 Q2 MATERIALS SCIENCE, BIOMATERIALS
Kun Wang, Jing Sun, Hongyu Zhang, Liang Li, Ning Zhang, Zhiqi Liu, Ming Shi, Jiexia Wen, Yimin Wang, Kun Li
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引用次数: 0

摘要

近年来,肿瘤的发病率呈上升趋势,而传统的手术、放疗、化疗等治疗方法存在一定的局限性。免疫疗法因其识别特异性高、明显抑制肿瘤生长和增殖、对正常组织细胞的结构和功能无不良影响等优点,在癌症治疗领域得到了广泛的研究。自然杀伤细胞(NK)作为先天免疫系统的重要组成部分,在抗肿瘤免疫应答中起着关键作用。本研究构建了一种装载NK细胞的磁性纳米载体,将磁性靶向与NK免疫治疗相结合。该系统将磁靶向与NK细胞免疫治疗相结合,通过外磁场引导增强NK细胞在肿瘤部位的浸润,从而提高杀伤肿瘤的效果。主要研究内容如下:制备纳米级Fe3O4@Agarose微球(AMbs)并进行羧化处理,得到粒径约为200nm的羧化Fe3O4@Agarose-COOH微球。以这些羧化微球为载体,偶联NK细胞上CD16表面蛋白对应的适配体MCD16,构建了“AMbs-MCD16-NK”磁性靶向体系。建立U14小鼠宫颈癌荷瘤模型,评价该体系的体内抗肿瘤疗效和生物安全性。结果表明,在磁场调节下,“AMbs-MCD16-NK”系统在肿瘤部位表现出优异的肿瘤靶向能力,对小鼠的肿瘤抑制率为57.32±12.98%。该系统有效抑制肿瘤细胞增殖,诱导肿瘤组织凋亡和坏死病变,促进NK细胞向肿瘤部位浸润,调节促炎细胞因子(如干扰素-γ (IFN-γ)和颗粒酶B (GZMB))的释放,从而增强NK细胞对肿瘤细胞的细胞毒性。小鼠体内一系列生物学指标的检测证实了“AMbs-MCD16-NK”体系具有良好的生物安全性。总之,本研究开发的“AMbs-MCD16-NK”系统通过磁靶向增强NK细胞免疫治疗,为NK细胞介导的癌症治疗提供了一种策略。
本文章由计算机程序翻译,如有差异,请以英文原文为准。
Research on the Effect of NK Cells Based on Functionalized Magnetic Beads on Cervical Cancer Mice.

In recent years, the incidence of tumors has shown an increasing trend, while traditional treatment methods such as surgery, radiotherapy, and chemotherapy exhibit certain limitations. Immunotherapy has been extensively investigated in the field of cancer treatment due to its advantages of high specificity in recognition, significant inhibition of tumor growth and proliferation, and the absence of adverse effects on the structure and function of normal tissue cells. Natural killer (NK) cells, as crucial components of the innate immune system, play a pivotal role in antitumor immune responses. In this study, a magnetic nanocarrier loaded with NK cells was constructed to combine magnetic targeting with NK immunotherapy. By integrating magnetic targeting with NK cell immunotherapy, this system enhances NK cell infiltration at tumor sites through external magnetic field guidance, thereby improving the tumor-killing efficacy. The main research contents are as follows: nanoscale Fe3O4@Agarose beads (AMbs) were fabricated and carboxylated to obtain carboxylated Fe3O4@Agarose-COOH beads with a particle size of approximately 200 nm. Using these carboxylated beads as carriers, the "AMbs-MCD16-NK" magnetic targeting system was constructed by conjugating the aptamer MCD16, which corresponds to the CD16 surface protein on NK cells. A U14 mouse cervical cancer tumor-bearing model was established to evaluate the in vivo antitumor efficacy and biosafety of the system. The results demonstrated that the "AMbs-MCD16-NK" system exhibited excellent tumor-targeting capability at the tumor site under magnetic field regulation, achieving a tumor inhibition rate of 57.32 ± 12.98% in mice. This system effectively inhibited tumor cell proliferation, induced apoptosis and necrotic lesions in tumor tissues, promoted NK cell infiltration into the tumor site, and regulated the release of proinflammatory cytokines (e.g., interferon-γ (IFN-γ) and granzyme B (GZMB)), thereby enhancing NK cell cytotoxicity against tumor cells. Detection of a series of biological indicators in mice confirmed that the "AMbs-MCD16-NK" system possessed favorable biosafety. Collectively, the "AMbs-MCD16-NK" system developed in this study enhances NK cell-based immunotherapy through magnetic targeting, providing a strategy for NK cell-mediated cancer treatment.

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来源期刊
ACS Applied Bio Materials
ACS Applied Bio Materials Chemistry-Chemistry (all)
CiteScore
9.40
自引率
2.10%
发文量
464
期刊介绍: ACS Applied Bio Materials is an interdisciplinary journal publishing original research covering all aspects of biomaterials and biointerfaces including and beyond the traditional biosensing, biomedical and therapeutic applications. The journal is devoted to reports of new and original experimental and theoretical research of an applied nature that integrates knowledge in the areas of materials, engineering, physics, bioscience, and chemistry into important bio applications. The journal is specifically interested in work that addresses the relationship between structure and function and assesses the stability and degradation of materials under relevant environmental and biological conditions.
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