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

一种用于细菌外膜囊泡分离和局部肿瘤免疫治疗的智能DNA水凝胶

作　　者：Rui Zhang Lele Chang Jing Wang Mengxue Huang Zhen Cui Siqi Li Jingwen Zhao Chi Yao Dayong Yang 张睿;常乐乐;王竞;黄梦雪;崔臻;李思齐;赵经文;姚池;仰大勇

机构地区：[1]Department of Chemistry,State Key Laboratory of Molecular Engineering of Polymers,Shanghai Key Laboratory of Molecular Catalysis and Innovative Materials,College of Chemistry and Materials,Fudan University,Shanghai 200438,China [2]Frontiers Science Center for Synthetic Biology,Key Laboratory of Systems Bioengineering(MOE),School of Chemical Engineering and Technology,Tianjin University,Tianjin 300350,China [3]Department of Gastroenterology and Hepatology,Tianjin Medical University General Hospital,Tianjin 300350,China

出　　处：《Science China Materials》2024年第12期3872-3884,共13页中国科学（材料科学）（英文版）

基　　金：supported by National Natural Science Foundation of China(22225505,22322407,and 22174097);Fudan University Ruiqing Education Funding。

摘　　要：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.细菌外膜囊泡(OMVs)在肿瘤免疫治疗中显示出巨大潜力.从复杂培养基中分离出高纯度和高生物活性的OMVs是应用于治疗的前提,但具有挑战性.本文报告了一种智能DNA水凝胶,用于从细菌培养基中高效分离OMVs,并进一步用于局部肿瘤免疫治疗.通过滚环扩增产生的两条超长DNA链交联构建DNA水凝胶.一条链含有多价GN6适配体,用于特异性捕获OMVs;另一条链含有多价PD-1适配体,用于阻断T淋巴细胞表面的PD-1免疫检查点.DNA水凝胶中包封的OMVs具有免疫刺激活性.在小鼠黑色素瘤模型中,含有OMVs的DNA水凝胶显示出显著的肿瘤抑制率(~95%).该智能DNA水凝胶为高效分离细菌来源的OMVs提供了平台化方案,助力肿瘤免疫治疗.

关 键 词：DNA nanotechnology DNA hydrogel bacterial outer membrane vesicles cancer immunotherapy 

分 类 号：R730.51[医药卫生—肿瘤] TQ427.26[医药卫生—临床医学]