A smart DNA hydrogel for isolation of bacterial outer membrane vesicles and localized cancer immunotherapy

IF 6.8 2区材料科学 Q1 MATERIALS SCIENCE, MULTIDISCIPLINARY Science China Materials Pub Date : 2024-10-21 DOI:10.1007/s40843-024-3094-9

Rui Zhang (, ), Lele Chang (, ), Jing Wang (, ), Mengxue Huang (, ), Zhen Cui (, ), Siqi Li (, ), Jingwen Zhao (, ), Chi Yao (, ), Dayong Yang (, )

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Abstract

Bacterial outer membrane vesicles (OMVs) have shown great potential in cancer immunotherapy. The isolation of OMVs from complex media with high purity and high bioactivity is the prerequisite of therapeutic applications, which remains highly challenging. Herein, we report a smart DNA hydrogel for the efficient isolation of OMVs from bacterial culture medium, which is further applied for localized cancer immunotherapy. The DNA hydrogel is constructed through the cross-linking of two ultralong DNA chains generated via rolling circle amplification (RCA). One chain contains polyvalent GN6 aptamer for the specific capture of OMVs, and the other contains polyvalent programmed death-1 (PD-1) aptamer for the blocking of PD-1 immune checkpoint on the surface of T lymphocytes. The OMVs capsulated by DNA hydrogel maintain high immunostimulatory bioactivity. In the mouse model of melanoma, this OMVs-containing DNA hydrogel shows a remarkable tumor inhibition rate of ∼95%. This smart DNA hydrogel represents a promising biomedical platform for the efficient isolation of bacterial-derived OMVs, and provides a powerful strategy for cancer immunotherapy.

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用于分离细菌外膜囊泡和局部癌症免疫疗法的智能 DNA 水凝胶

细菌外膜囊泡 (OMV) 在癌症免疫疗法中显示出巨大潜力。从复杂培养基中分离出高纯度、高生物活性的 OMVs 是治疗应用的先决条件，但这仍然极具挑战性。在此，我们报告了一种从细菌培养基中高效分离 OMVs 的智能 DNA 水凝胶，并将其进一步应用于局部癌症免疫疗法。这种 DNA 水凝胶是通过滚圆扩增（RCA）产生的两条超长 DNA 链交联而成的。其中一条DNA链含有多价GN6适配体，用于特异性捕获OMV；另一条DNA链含有多价程序性死亡-1（PD-1）适配体，用于阻断T淋巴细胞表面的PD-1免疫检查点。被 DNA 水凝胶包裹的 OMVs 可保持较高的免疫刺激生物活性。在黑色素瘤小鼠模型中，这种含有 OMVs 的 DNA 水凝胶对肿瘤的抑制率高达 95%。这种智能 DNA 水凝胶是高效分离细菌衍生 OMVs 的一种前景广阔的生物医学平台，为癌症免疫疗法提供了一种强有力的策略。

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来源期刊

Science China Materials Materials Science-General Materials Science

CiteScore

11.40

自引率

7.40%

发文量

949

期刊介绍： Science China Materials (SCM) is a globally peer-reviewed journal that covers all facets of materials science. It is supervised by the Chinese Academy of Sciences and co-sponsored by the Chinese Academy of Sciences and the National Natural Science Foundation of China. The journal is jointly published monthly in both printed and electronic forms by Science China Press and Springer. The aim of SCM is to encourage communication of high-quality, innovative research results at the cutting-edge interface of materials science with chemistry, physics, biology, and engineering. It focuses on breakthroughs from around the world and aims to become a world-leading academic journal for materials science.