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MgZnFe 层状双氢氧化物作为双功能平台增强肿瘤免疫治疗中的亚单位疫苗效力

英文原题:MgZnFe-layered double hydroxides as a dual-function platform for enhancing subunit vaccine efficacy in tumor immunotherapy.

查看英文原题

MgZnFe-layered double hydroxides as a dual-function platform for enhancing subunit vaccine efficacy in tumor immunotherapy.

PubMed 2025/09/01(内容时间) Int J Pharm X Q1 · IF 7.9(JCR 2025)

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中文摘要

治疗性癌症疫苗在免疫治疗中显示出前景,但面临抗原递送不佳、免疫激活不足和免疫抑制性肿瘤微环境等挑战,限制了肿瘤特异性细胞免疫。在本研究中,我们提出了一种双功能肿瘤疫苗平台MgFeZn-层状双氢氧化物(LMFZ),既作为抗原递送系统又作为免疫佐剂以增强抗肿瘤反应。负载抗原后,纳米级LMFZ颗粒高效转运至淋巴结,促进树突状细胞(DCs)对抗原的捕获。LMFZ的内体逃逸使抗原交叉呈递成为可能并增强DC成熟,促进细胞毒性T淋巴细胞增殖和肿瘤浸润。LMFZ还可中和肿瘤酸性、诱导巨噬细胞M1极化,并通过Zn 2+补充增强NK 细胞活性,从而放大抗肿瘤免疫。在小鼠模型中,经两次瘤周皮下注射后,负载抗原的LMFZ表现出显著抗肿瘤疗效且不良反应极小。这凸显了LMFZ疫苗平台临床转化的潜力,并为解决当前治疗性疫苗免疫疗法的局限性提供了创新策略。

展开英文摘要原文

Therapeutic cancer vaccines show promise in immunotherapy but face challenges such as poor antigen delivery, insufficient immune activation, and an immunosuppressive tumor microenvironment, limiting tumor-specific cellular immunity. In this study, we present a dual-function tumor vaccine platform, MgFeZn-Layered double hydroxide (LMFZ), serving as both an antigen delivery system and immune adjuvant to enhance antitumor responses. Loaded with antigens, nanometer-sized LMFZ particles efficiently traffic to lymph nodes, promoting antigen capture by dendritic cells (DCs).

LMFZ endosomal escape enables antigen cross-presentation and enhances DC maturation, boosting cytotoxic T lymphocyte proliferation and tumor infiltration. LMFZ also neutralizes tumor acidity, induces M1 polarization of macrophage, and enhances natural killer cell activity via Zn 2+ supplementation, amplifying antitumor immunity.

Following two peritumoral subcutaneous injections, antigen-loaded LMFZ demonstrated significant antitumor efficacy with minimal adverse effects in a mouse model. This highlights the potential of LMFZ vaccine platform for clinical translation and offers an innovative strategy to address the limitations of current therapeutic vaccine-based immunotherapies.

论文信息

作者
Wang X、Liu L、Chen Y、Jia L、Wang Y、Jing W、Yan G
单位
School and Hospital of Stomatology, Liaoning Provincial Key laboratory of Oral Diseases, China Medical University, Shenyang 110101, China.China
期刊
International journal of pharmaceutics: X2025 Dec
原文标识
PubMed 40978011 · DOI 10.1016/j.ijpx.2025.100384