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However, the biosafety and bioactivity of conventional hydrogel depots are often impaired by insufficient possibilities for post\u2010gelling injection and means for biofunction integration. Here, an unprecedented injectable stimuli\u2010responsive immunomodulatory depot through programming a super\u2010soft DNA\u00a0hydrogel adjuvant is reported. This hydrogel system encoded with adenosine triphosphate aptamers can be intratumorally injected in a gel formulation and then undergoes significant molecular conformation change to stimulate the distinct release kinetics of co\u2010encapsulated therapeutics. In this scenario, doxorubicin\u00a0is first released to induce immunogenic cell death that intimately works together with the polymerized cytosine\u2010phosphate\u2010guanine oligodeoxynucleotide (CpG ODN) in gel scaffold for effectively recruiting and activating dendritic cells. The polymerized CpG ODN not only enhances tumor immunogenicity but minimizes free CpG\u2010induced splenomegaly. Furthermore, the subsequently released anti\u2010programmed cell death protein ligand 1 (aPDL1) blocks the corresponding immune inhibitory checkpoint molecule on tumor cells to sensitize antitumor T\u2010cell immunity. This work thus contributes to the first proof\u2010of\u2010concept demonstration of a programmable super\u2010soft DNA hydrogel system that perfectly matches the synergistic therapeutic modalities based on chemotherapeutic toxicity, in situ vaccination, and immune checkpoint blockade.<\/jats:p>","DOI":"10.1002\/advs.202302119","type":"journal-article","created":{"date-parts":[[2023,8,4]],"date-time":"2023-08-04T19:05:00Z","timestamp":1691175900000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":39,"title":["Programming Injectable DNA Hydrogels Yields Tumor Microenvironment\u2010Activatable and Immune\u2010Instructive Depots for Augmented Chemo\u2010Immunotherapy"],"prefix":"10.1002","volume":"10","author":[{"ORCID":"https:\/\/orcid.org\/0000-0003-2197-4472","authenticated-orcid":false,"given":"Yu","family":"Fan","sequence":"first","affiliation":[{"name":"Department of Polymeric Materials School of Materials Science and Engineering Tongji University  Shanghai 201804 P. 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