pH 响应性锰颗粒通过多信号通路激活增强疫苗接种。
Multi-signaling pathway activation by pH responsive manganese particles for enhanced vaccination.
机构信息
Children's Hospital of Soochow University, Pediatric Research Institute of Soochow University, Suzhou, Jiangsu 215123, China.
Children's Hospital of Soochow University, Pediatric Research Institute of Soochow University, Suzhou, Jiangsu 215123, China.
出版信息
J Control Release. 2023 May;357:109-119. doi: 10.1016/j.jconrel.2023.01.078. Epub 2023 Mar 28.
As metal ions play important roles in the process of immunomodulation, immunotherapy based on metal ions has attracted tremendous interests in recent years. Here, we screened common metal ions and found that Mn could enhance the immune function in vitro. A new type of nanovaccine is thus fabricated by a biomimetic approach using nanoscale coordination polymer formed by Mn and 2-methylimidazole (2-MI) to encapsulate ovalbumin (OVA) protein, a model antigen, obtaining OVA@MM nanoparticles. Compared to free OVA, OVA@MM nanoparticles could more effectively induce the maturation of bone marrow-derived dendritic cells (BMDCs) and their subsequent antigen cross-presentation. The particles made of Mn and 2-MI could activate immune-regulated signal pathways to enhance the immune functions of BMDCs. Such OVA@MM nanovaccine could not only provide prophylactic effect to inhibit the growth of B16-OVA tumor on immunized mice, but also significantly inhibit tumor growth in the mice with B16-OVA tumor combined with anti-programmed cell death protein 1 (anti-PD-1) antibody. Therefore, this nanovaccine platform based on Mn, 2-MI and antigen may provide a simple, effective and broadly applicable strategy to enhance adaptive immunity against cancer and other diseases.
由于金属离子在免疫调节过程中发挥着重要作用，基于金属离子的免疫疗法近年来引起了极大的关注。在这里，我们筛选了常见的金属离子，发现 Mn 可以增强体外的免疫功能。因此，我们采用仿生方法制备了一种新型纳米疫苗，该方法使用由 Mn 和 2-甲基咪唑（2-MI）形成的纳米级配位聚合物来包裹卵清蛋白（OVA）作为模型抗原，得到 OVA@MM 纳米颗粒。与游离 OVA 相比，OVA@MM 纳米颗粒可以更有效地诱导骨髓来源树突状细胞（BMDCs）的成熟及其随后的抗原交叉呈递。Mn 和 2-MI 制成的颗粒可以激活免疫调节信号通路，增强 BMDCs 的免疫功能。这种 OVA@MM 纳米疫苗不仅可以对免疫小鼠的 B16-OVA 肿瘤生长起到预防作用，而且还可以显著抑制伴有抗程序性细胞死亡蛋白 1（抗-PD-1）抗体的 B16-OVA 肿瘤小鼠的肿瘤生长。因此，基于 Mn、2-MI 和抗原的这种纳米疫苗平台可能为增强针对癌症和其他疾病的适应性免疫提供了一种简单、有效且广泛适用的策略。
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