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一种经析因设计优化的微流控脂质纳米颗粒疫苗引发强效镁佐剂癌症免疫疗法。

A factorial design-optimized microfluidic LNP vaccine elicits potent magnesium-adjuvating cancer immunotherapy.

作者信息

Xie Yongyi, Guo Jiaxin, Hu Jialin, Li Yuan, Zhang Zhongqian, Zhu Yongcheng, Deng Fei, Qi Jialong, Zhou You, Chen Wenjie

机构信息

Guangzhou Municipal and Guangdong Provincial Key Laboratory of Molecular Target & Clinical Pharmacology, the NMPA and State Key Laboratory of Respiratory Disease, School of Pharmaceutical Sciences, Guangzhou Medical University, Guangzhou, 511436, PR China.

Department of Emergency, The Second Affiliated Hospital, Guangzhou Medical University, Guangzhou, 510260, PR China.

出版信息

Mater Today Bio. 2025 Mar 24;32:101703. doi: 10.1016/j.mtbio.2025.101703. eCollection 2025 Jun.

DOI:10.1016/j.mtbio.2025.101703
PMID:40230646
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC11994397/
Abstract

Human papillomavirus (HPV)-associated cancers remain a critical health challenge, prompting the development of effective therapeutic vaccines. This study presents a lipid nanoparticle (LNP)-based vaccine co-loading E7 antigen peptide and magnesium ions as the adjuvant. Microfluidic technology was employed to optimize LNP preparation and formulation, ensuring efficient co-delivery of antigen and adjuvant. Magnesium ions were chosen over conventional aluminum-based adjuvants, which often suffer from limited efficacy and adverse effects, particularly for cancer immunotherapy. Compared to aluminum, magnesium ions exhibited superior capabilities in enhancing T-cell activation and promoting cellular immune response. Mechanistic insights suggest that magnesium ions facilitate dendritic cell maturation and antigen presentation via a collagen-CD36 axis, contributing to the adjuvant activity of magnesium. Through design of experiments (DoE) optimization, the LNP formulation was tailored for enhanced encapsulation and stability, positioning it as a targeted system for immune activation. These findings support the promise of magnesium ions as effective and safer adjuvants in LNP-based vaccines, marking a potential advancement for therapeutic cancer vaccination.

摘要

人乳头瘤病毒（HPV）相关癌症仍然是一项严峻的健康挑战，这促使人们开发有效的治疗性疫苗。本研究提出了一种基于脂质纳米颗粒（LNP）的疫苗，该疫苗共负载E7抗原肽和镁离子作为佐剂。采用微流控技术优化LNP的制备和配方，确保抗原和佐剂的高效共递送。与传统的铝基佐剂相比，镁离子被选用，铝基佐剂常常疗效有限且有不良反应，尤其是在癌症免疫治疗中。与铝相比，镁离子在增强T细胞活化和促进细胞免疫反应方面表现出卓越的能力。机制研究表明，镁离子通过胶原-CD36轴促进树突状细胞成熟和抗原呈递，这有助于镁的佐剂活性。通过实验设计（DoE）优化，LNP配方经过调整以提高包封率和稳定性，使其成为免疫激活的靶向系统。这些发现支持了镁离子作为基于LNP的疫苗中有效且更安全佐剂的前景，标志着治疗性癌症疫苗接种的潜在进展。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/f3a9/11994397/0341655c7554/gr9.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/f3a9/11994397/727140f65f10/ga1.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/f3a9/11994397/b4ba65f9e802/gr1.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/f3a9/11994397/822abcd0cd4a/gr2.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/f3a9/11994397/1e42ed1ec695/gr3.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/f3a9/11994397/5b36f342a45a/gr4.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/f3a9/11994397/d174f3ebbdb0/gr5.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/f3a9/11994397/0754396494db/gr6.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/f3a9/11994397/acdb1e5476db/gr7.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/f3a9/11994397/d6ffa63fa622/gr8.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/f3a9/11994397/0341655c7554/gr9.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/f3a9/11994397/727140f65f10/ga1.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/f3a9/11994397/b4ba65f9e802/gr1.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/f3a9/11994397/822abcd0cd4a/gr2.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/f3a9/11994397/1e42ed1ec695/gr3.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/f3a9/11994397/5b36f342a45a/gr4.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/f3a9/11994397/d174f3ebbdb0/gr5.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/f3a9/11994397/0754396494db/gr6.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/f3a9/11994397/acdb1e5476db/gr7.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/f3a9/11994397/d6ffa63fa622/gr8.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/f3a9/11994397/0341655c7554/gr9.jpg

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本文引用的文献

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Spleen-Targeted mRNA Vaccine Doped with Manganese Adjuvant for Robust Anticancer Immunity .脾脏靶向 mRNA 疫苗联合锰佐剂增强抗肿瘤免疫
ACS Nano. 2024 Nov 5;18(44):30701-30715. doi: 10.1021/acsnano.4c09902. Epub 2024 Oct 28.
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Optimized microfluidic formulation and organic excipients for improved lipid nanoparticle mediated genome editing.
优化的微流体制剂和有机辅料可提高脂质纳米颗粒介导的基因组编辑效率。
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A narrative review on the role of magnesium in immune regulation, inflammation, infectious diseases, and cancer.一篇关于镁在免疫调节、炎症、传染病和癌症中的作用的叙述性综述。
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Vaccine adjuvants: mechanisms and platforms.疫苗佐剂：作用机制与平台。
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Research Progress of Aluminum Phosphate Adjuvants and Their Action Mechanisms.磷酸铝佐剂及其作用机制的研究进展
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T cells in health and disease.健康与疾病中的 T 细胞。
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