A smart DNA hydrogel for isolation of bacterial outer membrane vesicles and localized cancer immunotherapy
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 bac-terial culture medium,which is further applied for localized cancer immunotherapy.The DNA hydrogel is constructed through the cross-linking of two ultralong DNA chains gen-erated via rolling circle amplification(RCA).One chain con-tains 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 check-point on the surface of T lymphocytes.The OMVs capsulated by DNA hydrogel maintain high immunostimulatory bioac-tivity.In the mouse model of melanoma,this OMVs-con-taining DNA hydrogel shows a remarkable tumor inhibition rate of~95%.This smart DNA hydrogel represents a pro-mising biomedical platform for the efficient isolation of bac-terial-derived OMVs,and provides a powerful strategy for cancer immunotherapy.
DNA nanotechnologyDNA hydrogelbacterial outer membrane vesiclescancer immunotherapy
张睿、常乐乐、王竞、黄梦雪、崔臻、李思齐、赵经文、姚池、仰大勇
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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
Frontiers Science Center for Synthetic Biology,Key Laboratory of Systems Bioengineering(MOE),School of Chemical Engineering and Technology,Tianjin University,Tianjin 300350,China
Department of Gastroenterology and Hepatology,Tianjin Medical University General Hospital,Tianjin 300350,China
DNA nanotechnology DNA hydrogel bacterial outer membrane vesicles cancer immunotherapy