Xie Yongyi, Guo Jiaxin, Hu Jialin, Li Yuan, Zhang Zhongqian, Zhu Yongcheng, Deng Fei, Qi Jialong, Zhou You, Chen Wenjie
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.
Mater Today Bio. 2025 Mar 24;32:101703. doi: 10.1016/j.mtbio.2025.101703. eCollection 2025 Jun.
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.
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。
