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基于功能化磁珠的 NK 细胞对宫颈癌小鼠作用的研究

英文原题:Research on the Effect of NK Cells Based on Functionalized Magnetic Beads on Cervical Cancer Mice.

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Research on the Effect of NK Cells Based on Functionalized Magnetic Beads on Cervical Cancer Mice.

PubMed 2025/10/03(内容时间) ACS Appl Bio Mater Q2 · IF 5.6(JCR 2025)

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中文摘要

近年来肿瘤发病率呈上升趋势,而手术、放疗和化疗等传统治疗方法存在一定局限。免疫治疗因识别特异性高、显著抑制肿瘤生长和增殖、且不损害正常组织细胞结构和功能等优势,在癌症治疗领域得到广泛研究。自然杀伤(NK)细胞是先天免疫系统的重要组成部分,在抗肿瘤免疫应答中发挥关键作用。

本研究构建了一种负载NK细胞的磁性纳米载体,将磁靶向与NK免疫治疗结合。该系统在外部磁场引导下增强NK细胞向肿瘤部位浸润,从而提高肿瘤杀伤效力。研究主要内容如下:制备纳米级Fe3O4@琼脂糖微珠(AMbs),并进行羧基化,得到粒径约200 nm的Fe3O4@琼脂糖-COOH微珠。以羧基化微珠为载体,通过偶联适配体MCD16(其对应NK细胞表面蛋白CD16),构建“AMbs-MCD16-NK”磁靶向系统。建立U14小鼠宫颈癌荷瘤模型,评估其体内抗肿瘤疗效和生物安全性。

结果显示,在磁场调控下,“AMbs-MCD16-NK”系统具有优异的肿瘤靶向能力,小鼠肿瘤抑制率为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灶,促进NK细胞浸润肿瘤部位,并调节促炎细胞因子(如干扰素γ〔IFN-γ〕和颗粒酶B〔GZMB〕)释放,从而增强NK细胞对肿瘤细胞的细胞毒作用。对小鼠多项生物学指标的检测证实,该系统具有良好生物安全性。

综上,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。

展开英文摘要原文

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 Fe 3 O 4 @Agarose beads (AMbs) were fabricated and carboxylated to obtain carboxylated Fe 3 O 4 @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- (IFN- ) 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.

论文信息

作者
Wang K、Sun J、Zhang H、Li L、Zhang N、Liu Z、Shi M、Wen J
单位
College of Environmental & Chemical Engineering, Yanshan University, Qinhuangdao, Hebei Province 066004, China.China
期刊
ACS applied bio materials2025 Oct 20
原文标识
PubMed 41042015 · DOI 10.1021/acsabm.5c00811