There is a need for effective vaccine delivery systems and vaccine adjuvants without extraneous excipients that can compromise or minimize their efficacy. Vaccine adjuvants cytosine–phosphate–guanosine oligodeoxynucleotides (CpG ODNs) can effectively activate immune responses to secrete cytokines. However, CpG ODNs are not stable in serum due to enzymatic cleavage and are difficult to transport through cell membranes. Herein, DNA microcapsules made of CpG ODNs arranged into 3D nanostructures are developed to improve the serum stability and immunostimulatory effect of CpG. The DNA microcapsules allow encapsulation and co‐delivery of cargoes, including glycogen. The DNA capsules, with >4 million copies of CpG motifs per capsule, are internalized in cells and accumulate in endosomes, where the Toll‐like receptor 9 is engaged by CpG. The capsules induce up to 10‐fold and 20‐fold increases in tumor necrosis factor (TNF)‐α and interleukin (IL)‐6 secretion, respectively, in RAW264.7 cells compared with CpG ODNs. Furthermore, the microcapsules stimulate TNF‐α and IL‐6 secretion in a concentration‐ and time‐dependent manner. The immunostimulatory activity of the capsules correlates to their intracellular trafficking, endosomal confinement, and degradation, assessed by confocal and super‐resolution microscopy. These DNA capsules can serve as both adjuvants to stimulate an immune reaction and vehicles to encapsulate vaccine peptides/genes to achieve synergistic immune effects.

中文翻译：

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模板介导的DNA组装成微胶囊的免疫调节。

需要有效的疫苗递送系统和疫苗佐剂，而没有会损害或最小化其功效的外来赋形剂。疫苗佐剂胞嘧啶-磷酸-鸟苷寡聚脱氧核苷酸（CpG ODN）可以有效激活免疫应答以分泌细胞因子。然而，由于酶促裂解，CpG ODN在血清中不稳定，并且难以通过细胞膜转运。在本文中，开发了由排列成3D纳米结构的CpG ODN制成的DNA微胶囊，以改善CpG的血清稳定性和免疫刺激作用。DNA微胶囊可以包裹和共输送货物，包括糖原。DNA胶囊每个胶囊具有超过400万个CpG基序拷贝，被细胞内化并积聚在内体中，在那里Toll样受体9被CpG参与。与CpG ODN相比，该胶囊在RAW264.7细胞中分别诱导肿瘤坏死因子（TNF）-α和白介素（IL）-6分泌分别增加10倍和20倍。此外，微胶囊以浓度和时间依赖的方式刺激TNF-α和IL-6的分泌。通过共聚焦和超高分辨率显微镜评估，胶囊的免疫刺激活性与其细胞内运输，内体限制和降解相关。这些DNA胶囊既可以充当佐剂来刺激免疫反应，又可以充当载体来封装疫苗肽/基因以实现协同免疫效果。微胶囊以浓度和时间依赖的方式刺激TNF-α和IL-6的分泌。通过共聚焦和超高分辨率显微镜评估，胶囊的免疫刺激活性与其细胞内运输，内体限制和降解相关。这些DNA胶囊既可以充当佐剂来刺激免疫反应，又可以充当载体来封装疫苗肽/基因以实现协同免疫效果。微胶囊以浓度和时间依赖的方式刺激TNF-α和IL-6的分泌。通过共聚焦和超高分辨率显微镜评估，胶囊的免疫刺激活性与其细胞内运输，内体限制和降解相关。这些DNA胶囊既可以充当佐剂来刺激免疫反应，又可以充当载体来封装疫苗肽/基因以实现协同免疫效果。