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

IF 6.4 2区医学 Q1 PHARMACOLOGY & PHARMACY

International Journal of Pharmaceutics: X Pub Date : 2025-09-01 DOI:10.1016/j.ijpx.2025.100384

Xue Wang , Lu Liu , Yingying Chen , Lirui Jia , Yongjun Wang , Wei Jing , Guangqi Yan

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Abstract

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 Zn²⁺ 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.

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mgznfe层状双氢氧化物作为增强肿瘤免疫治疗亚单位疫苗效力的双重功能平台

治疗性癌症疫苗在免疫治疗中显示出希望，但面临着诸如抗原递送不良、免疫激活不足和免疫抑制肿瘤微环境等挑战，限制了肿瘤特异性细胞免疫。在这项研究中，我们提出了一种双重功能的肿瘤疫苗平台，mgfezn -层状双氢氧化物（LMFZ），作为抗原递送系统和免疫佐剂来增强抗肿瘤反应。纳米大小的LMFZ颗粒装载抗原，有效地运输到淋巴结，促进抗原被树突状细胞（dc）捕获。LMFZ内体逃逸使抗原交叉呈递，促进DC成熟，促进细胞毒性T淋巴细胞增殖和肿瘤浸润。LMFZ还能中和肿瘤酸性，诱导巨噬细胞M1极化，并通过补充Zn2+增强自然杀伤细胞活性，增强抗肿瘤免疫。在两次瘤周皮下注射后，抗原负载的LMFZ在小鼠模型中显示出显著的抗肿瘤功效，副作用最小。这突出了LMFZ疫苗平台在临床转化方面的潜力，并为解决当前基于疫苗的治疗性免疫疗法的局限性提供了一种创新策略。

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来源期刊

International Journal of Pharmaceutics: X Pharmacology, Toxicology and Pharmaceutics-Pharmaceutical Science

CiteScore

6.60

自引率

0.00%

发文量

审稿时长

24 days

期刊介绍： International Journal of Pharmaceutics: X offers authors with high-quality research who want to publish in a gold open access journal the opportunity to make their work immediately, permanently, and freely accessible. International Journal of Pharmaceutics: X authors will pay an article publishing charge (APC), have a choice of license options, and retain copyright. Please check the APC here. The journal is indexed in SCOPUS, PUBMED, PMC and DOAJ. The International Journal of Pharmaceutics is the second most cited journal in the "Pharmacy & Pharmacology" category out of 358 journals, being the true home for pharmaceutical scientists concerned with the physical, chemical and biological properties of devices and delivery systems for drugs, vaccines and biologicals, including their design, manufacture and evaluation. This includes evaluation of the properties of drugs, excipients such as surfactants and polymers and novel materials. The journal has special sections on pharmaceutical nanotechnology and personalized medicines, and publishes research papers, reviews, commentaries and letters to the editor as well as special issues.