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IF: 27.4
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Spatiotemporal Nano‐Regulator Unleashes Anti‐Tumor Immunity by Overcoming Dendritic Cell Tolerance and T Cell Exhaustion in Tumor‐Draining Lymph Nodes

Published:11 December 2024 DOI: 10.1002/adma.202412141
Ruonan Wang, Huixin Li, Shasha He, Yuanji Feng, Cong Liu, Kai Hao, Danhua Zhou, Xiaoyuan Chen, Huayu Tian

Abstract

Lymph nodes are crucial immune foci as the primary target for cancer immunotherapy. However, the anti-tumor functions of tumor-draining lymph nodes (TDLNs) are critically suppressed by tumors. Here, a novel spatiotemporal nano-regulator is presented, designed to modulate the dendritic cells (DCs) in TDLNs, establishing a supportive niche for immune surveillance. The DC-mediated nano-regulator (DNR) is established by the self-assembly 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-targeting siRNA mitigates the tolerogenic effects induced by tumor-derived factors and TLR activation, preventing T cell exhaustion. In essence, DNR facilitates potent remodeling of TDLNs and the tumor microenvironment, activating the anti-tumor immunity cascade. When combined with vaccines, DNR greatly promotes tumor regression and the establishment of long-term immunological memory.

Substances (8)

Materials
Procduct Name CAS Molecular Formula Supplier Price
Ethylenediaminetetraacetic acid 60-00-4 C10H16N2O8 1439 suppliers $6.00-$6397.62
Triethylamine 121-44-8 C6H15N 1019 suppliers $9.00-$2730.00
4-Carboxyphenylboronic acid 14047-29-1 C7H7BO4 588 suppliers $4.00-$666.40
3-Carboxyphenylboronic acid 25487-66-5 C7H7BO4 574 suppliers $6.00-$899.00
Fluorescein isothiocyanate isomer I 3326-32-7 C21H11NO5S 558 suppliers $16.00-$8352.40
Triphosgene 32315-10-9 C3Cl6O3 497 suppliers $10.00-$4341.65
2-Carboxyphenylboronic acid 149105-19-1 C7H7BO4 330 suppliers $7.62-$2167.00
HYDROXYLAMINE 7803-49-8 H3NO 274 suppliers $14.00-$4112.61

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