Tang Jie, Yang Yang, Qu Jingjing, Ban Wenhuang, Song Hao, Gu Zhengying, Yang Yannan, Cai Larry, Theivendran Shevanuja, Wang Yue, Zhang Min, Yu Chengzhong
Australian Institute for Bioengineering and Nanotechnology, The University of Queensland St Lucia Brisbane QLD 4072 Australia
School of Chemistry and Molecular Engineering, East China Normal University Shanghai 200241 China
Chem Sci. 2022 Jul 20;13(29):8507-8517. doi: 10.1039/d1sc05319a. eCollection 2022 Jul 29.
Pyroptosis is a programmed cell death widely studied in cancer cells for tumour inhibition, but rarely in dendritic cell (DC) activation for vaccine development. Here, we report the synthesis of sodium stabilized mesoporous aluminosilicate nanoparticles as DC pyroptosis modulators and antigen carriers. By surface modification of sodium-stabilized four-coordinate aluminium species on dendritic mesoporous silica nanoparticles, the resultant Na-Al-DMSN significantly activated DC through caspase-1 dependent pyroptosis pH responsive intracellular ion exchange. The released proinflammatory cellular contents further mediated DC hyperactivation with prolonged cytokine release. studies showed that Na-Al-DMSN induced enhanced cellular immunity mediated by natural killer (NK) cells, cytotoxic T cells, and memory T cells as well as humoral immune response. Our results provide a new principle for the design of next-generation nanoadjuvants for vaccine applications.
焦亡是一种程序性细胞死亡，在癌细胞中因肿瘤抑制作用而被广泛研究，但在用于疫苗开发的树突状细胞（DC）激活方面研究较少。在此，我们报告了合成钠稳定的介孔硅铝酸盐纳米颗粒作为DC焦亡调节剂和抗原载体。通过在树枝状介孔二氧化硅纳米颗粒上对钠稳定的四配位铝物种进行表面修饰，所得的Na-Al-DMSN通过半胱天冬酶-1依赖性焦亡pH响应性细胞内离子交换显著激活DC。释放的促炎细胞内容物进一步介导DC过度激活并延长细胞因子释放。研究表明，Na-Al-DMSN诱导由自然杀伤（NK）细胞、细胞毒性T细胞和记忆T细胞介导的增强的细胞免疫以及体液免疫反应。我们的结果为设计用于疫苗应用的下一代纳米佐剂提供了新原理。
