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However, the anti\u2010tumor functions of tumor\u2010draining lymph nodes (TDLNs) are critically suppressed by tumors. Here, a novel spatiotemporal nano\u2010regulator is presented, designed to modulate the dendritic cells (DCs) in TDLNs, establishing a supportive niche for immune surveillance. The DC\u2010mediated nano\u2010regulator (DNR) is established by the self\u2010assembly of an imidazoquinoline (IMDQ) prodrug, inhibitory immune checkpoint (ICP) siRNA, and mannan (a TLR4 agonist). This unique design leverages the spatiotemporal activation of TLR4 and TLR7\/8, thereby optimizing DC maturation and cytokine production. This further promotes efficient T cell priming. Simultaneously, the ICP\u2010targeting siRNA mitigates the tolerogenic effects induced by tumor\u2010derived factors and TLR activation, preventing T cell exhaustion. In essence, DNR facilitates potent remodeling of TDLNs and the tumor microenvironment, activating the anti\u2010tumor immunity cascade. When combined with vaccines, DNR greatly promotes tumor regression and the establishment of long\u2010term immunological memory.<\/jats:p>","DOI":"10.1002\/adma.202412141","type":"journal-article","created":{"date-parts":[[2024,12,12]],"date-time":"2024-12-12T01:26:47Z","timestamp":1733966807000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":18,"title":["Spatiotemporal Nano\u2010Regulator Unleashes Anti\u2010Tumor Immunity by Overcoming Dendritic Cell Tolerance and T Cell Exhaustion in Tumor\u2010Draining Lymph Nodes"],"prefix":"10.1002","volume":"37","author":[{"ORCID":"https:\/\/orcid.org\/0009-0008-7567-4049","authenticated-orcid":false,"given":"Ruonan","family":"Wang","sequence":"first","affiliation":[{"name":"State Key Laboratory of Physical Chemistry of Solid Surfaces College of Chemistry and Chemical Engineering Xiamen University  Xiamen 361005 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