Zeolitic Imidazolate Framework Nanoencapsulation of CpG for Stabilization and Enhancement of Immunoadjuvancy
Zeolitic Imidazolate Framework Nanoencapsulation of CpG for Stabilization and Enhancement of Immunoadjuvancy
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DOI：
10.1021/acsanm.1c03555
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发表时间：
2022-01-12
影响因子：
5.9
通讯作者：
Gassensmith, Jeremiah J.
中科院分区：
文献类型：
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作者：
Brohlin, Olivia R.;Ehrman, Ryanne N.;Gassensmith, Jeremiah J.
金属有机骨架(MOF)已被用于通过稳定蛋白质和保护它们免受热降解来改进疫苗配方。这导致了这些蛋白质疗法的免疫原性增加。在这项工作中，我们发现MOF还可以用来保护单链DNA寡聚体CpG，以增加其免疫佐剂。通过将磷酸二酯CpG包裹在锌基MOF中，即沸石咪唑骨架-8，DNA寡聚物可防止核酸酶降解，并显示出改善的细胞摄取。因此，我们能够在脾细胞培养中显著增强B细胞的激活，与传统的免疫增强剂相比，我们已经对微米和纳米级的MOF进行了直接比较，以优化免疫佐剂的微粒输送，以最大限度地激活免疫。
Metal-organic frameworks (MOFs) have been used to improve vaccine formulations by stabilizing proteins and protecting them against thermal degradation. This has led to increased immunogenicity of these proteinaceous therapeutics. In this work, we show that MOFs can also be used to protect the single-stranded DNA oligomer CpG to increase its immunoadjuvancy. By encapsulation of the phosphodiester CpG in the zincbased MOF, zeolitic imidazolate framework-8, the DNA oligomer is protected from nuclease degradation and exhibits improved cellular uptake. As a result, we have been able to achieve drastically enhanced B-cell activation in splenocyte cultures comparable to the have made a direct comparison of micro- and nanosized MOFs for optimization of the particulate delivery of immunoadjuvants to maximize immune activation.