Tumor Microenvironment‐Responsive Nanoparticles Enhance IDO1 Blockade Immunotherapy by Remodeling Metabolic Immunosuppression Article Swipe
Mengna Wang
,
Jinjin Li
,
Yanshi Li
,
Tao Lü
,
Min Wang
,
Zhaobo Cheng
,
Lin Chen
,
Tongling Wen
,
Min Pan
,
Guohua Hu
·
YOU?
·
· 2024
· Open Access
·
· DOI: https://doi.org/10.1002/advs.202405845
YOU?
·
· 2024
· Open Access
·
· DOI: https://doi.org/10.1002/advs.202405845
The clinical efficacy of immune checkpoint blockade (ICB) therapy is significantly compromised in the metabolically disordered tumor microenvironment (TME), posing a formidable challenge that cannot be ignored in current antitumor strategies. In this study, TME‐responsive nanoparticles (HMP1G NPs) loaded with 1‐methyltryptophan (1‐MT; an indoleamine 2,3‐dioxygenase 1 [IDO1] inhibitor,) and S‐nitrosoglutathione (GSNO; a nitric oxide donor) is developed to enhance the therapeutic efficacy of 1‐MT‐mediated ICB. The HMP1G NPs responded to H + and glutathione in the TME, releasing Mn 2+ , GSNO, and 1‐MT. The released Mn 2+ catalyzed the production of abundant reactive oxygen species and nitric oxide from hydrogen peroxide and GSNO, and the generated nitric oxide, synergistically with 1‐MT, inhibited the accumulation of kynurenine mediated by IDO1 in the tumor. Mechanistically, HMP1G NPs downregulated tumor cell‐derived IDO1 via the aryl hydrocarbon receptor/signal transducer and activator of transcription 3/interleukin signaling axis to improve kynurenine/tryptophan metabolism and immunosuppression. In a murine breast cancer model, treatment with HMP1G NPs elicited effective antitumor immunity and enhanced survival outcomes. This study highlights a novel nano‐platform that simultaneously improves metabolism and enhances ICB efficacy to achieve a new and efficient antitumor strategy.
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Metadata
- Type
- article
- Language
- en
- Landing Page
- https://doi.org/10.1002/advs.202405845
- OA Status
- gold
- Cited By
- 11
- References
- 32
- Related Works
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- OpenAlex ID
- https://openalex.org/W4405279073
All OpenAlex metadata
Raw OpenAlex JSON
- OpenAlex ID
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https://openalex.org/W4405279073Canonical identifier for this work in OpenAlex
- DOI
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https://doi.org/10.1002/advs.202405845Digital Object Identifier
- Title
-
Tumor Microenvironment‐Responsive Nanoparticles Enhance IDO1 Blockade Immunotherapy by Remodeling Metabolic ImmunosuppressionWork title
- Type
-
articleOpenAlex work type
- Language
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enPrimary language
- Publication year
-
2024Year of publication
- Publication date
-
2024-12-11Full publication date if available
- Authors
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Mengna Wang, Jinjin Li, Yanshi Li, Tao Lü, Min Wang, Zhaobo Cheng, Lin Chen, Tongling Wen, Min Pan, Guohua HuList of authors in order
- Landing page
-
https://doi.org/10.1002/advs.202405845Publisher landing page
- Open access
-
YesWhether a free full text is available
- OA status
-
goldOpen access status per OpenAlex
- OA URL
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https://doi.org/10.1002/advs.202405845Direct OA link when available
- Concepts
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Blockade, Tumor microenvironment, Immunosuppression, Nitric oxide, Immunotherapy, Cancer research, Immune checkpoint, Immune system, Chemistry, Medicine, Pharmacology, Immunology, Receptor, Internal medicine, BiochemistryTop concepts (fields/topics) attached by OpenAlex
- Cited by
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11Total citation count in OpenAlex
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2025: 11Per-year citation counts (last 5 years)
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32Number of works referenced by this work
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10Other works algorithmically related by OpenAlex
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