Dendritic Nanomedicine with Boronate Bonds for Augmented Chemo-Immunotherapy via Synergistic Modulation of Tumor Immune Microenvironment

© 2023 Wiley-VCH GmbH.

Détails bibliographiques
Publié dans:Advanced materials (Deerfield Beach, Fla.). - 1998. - 36(2024), 2 vom: 06. Jan., Seite e2307263
Auteur principal: Li, Yunkun (Auteur)
Autres auteurs: Wu, Yahui, Fang, Zaixiang, Zhang, Yuxin, Ding, Haitao, Ren, Long, Zhang, Lu, Gong, Qiyong, Gu, Zhongwei, Luo, Kui
Format: Article en ligne
Langue:English
Publié: 2024
Accès à la collection:Advanced materials (Deerfield Beach, Fla.)
Sujets:Journal Article IDO inhibition chemo-immunotherapy dendritic drug delivery system tumor immune microenvironment reeducation Epirubicin 3Z8479ZZ5X Tryptophan 8DUH1N11BX
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520 |a Unsatisfied tumor accumulation of chemotherapeutic drugs and a complicated immunosuppressive microenvironment diminish the immune response rate and the therapeutic effect. Surface modification of these drugs with target ligands can promote their cellular internalization, but the modified drugs may be subjected to unexpected immune recognition and clearance. Herein, a phenylboronic acid (PBA) group-shieldable dendritic nanomedicine that integrates an immunogenic cell death (ICD)-inducing agent (epirubicin, Epi) and an indoleamine 2,3-dioxgenase 1 (IDO1) inhibitor (NLG919) is reported for tumor chemo-immunotherapy. This NLG919-loaded Epi-conjugated PEGylated dendrimers bridged with boronate bonds (NLG919Epi-DBP) maintains a stable nanostructure during circulation. Under a moderate acidic condition, the PBA group exposes to the sialic acid residue on the tumor cell membrane to enhance the internalization and penetration of NLG919@Epi-DBP. At pH 5.0, NLG919@Epi-DBP rapidly disassembles to release the incorporated Epi and NLG919. Epi triggers robust ICD of tumor cells that evokes strong immune response. In addition, inhibition of the IDO1 activity downregulates the metabolism of L-tryptophan to kynurenine, leading to a reduction in the recruitment of immunosuppressive cells and modulation of the tumor immune microenvironment. Collectively, this promising strategy has been demonstrated to evoke robust immune response as well as remodel the immunosuppressive microenvironment for an enhanced chemo-immunotherapeutic effect 
650 4 |a Journal Article 
650 4 |a IDO inhibition 
650 4 |a chemo-immunotherapy 
650 4 |a dendritic drug delivery system 
650 4 |a tumor immune microenvironment reeducation 
650 7 |a Epirubicin  |2 NLM 
650 7 |a 3Z8479ZZ5X  |2 NLM 
650 7 |a Tryptophan  |2 NLM 
650 7 |a 8DUH1N11BX  |2 NLM 
700 1 |a Wu, Yahui  |e verfasserin  |4 aut 
700 1 |a Fang, Zaixiang  |e verfasserin  |4 aut 
700 1 |a Zhang, Yuxin  |e verfasserin  |4 aut 
700 1 |a Ding, Haitao  |e verfasserin  |4 aut 
700 1 |a Ren, Long  |e verfasserin  |4 aut 
700 1 |a Zhang, Lu  |e verfasserin  |4 aut 
700 1 |a Gong, Qiyong  |e verfasserin  |4 aut 
700 1 |a Gu, Zhongwei  |e verfasserin  |4 aut 
700 1 |a Luo, Kui  |e verfasserin  |4 aut 
773 0 8 |i Enthalten in  |t Advanced materials (Deerfield Beach, Fla.)  |d 1998  |g 36(2024), 2 vom: 06. Jan., Seite e2307263  |w (DE-627)NLM098206397  |x 1521-4095  |7 nnas 
773 1 8 |g volume:36  |g year:2024  |g number:2  |g day:06  |g month:01  |g pages:e2307263 
856 4 0 |u http://dx.doi.org/10.1002/adma.202307263  |3 Volltext 
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