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Tumor microenvironment-responsive micelles assembled from a prodrug of mitoxantrone and 1-methyl tryptophan for enhanced chemo-immunotherapy

Mitoxantrone (MX) can induce the immunogenic-cell death (ICD) of tumor cells and activate anti-tumor immune responses. However, it can also cause high expression of indole amine 2, 3-dioxygenase (IDO) during ICD, leading to T-cell apoptosis and a weakened immune response. An IDO inhibitor, 1-methyl...

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Autores principales: Wang, Ru, Li, Nuannuan, Zhang, Tianyu, Sun, Yiying, He, Xiaoyan, Lu, Xiaoyan, Chu, Liuxiang, Sun, Kaoxiang
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Taylor & Francis 2023
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9970211/
https://www.ncbi.nlm.nih.gov/pubmed/36840464
http://dx.doi.org/10.1080/10717544.2023.2182254
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author Wang, Ru
Li, Nuannuan
Zhang, Tianyu
Sun, Yiying
He, Xiaoyan
Lu, Xiaoyan
Chu, Liuxiang
Sun, Kaoxiang
author_facet Wang, Ru
Li, Nuannuan
Zhang, Tianyu
Sun, Yiying
He, Xiaoyan
Lu, Xiaoyan
Chu, Liuxiang
Sun, Kaoxiang
author_sort Wang, Ru
collection PubMed
description Mitoxantrone (MX) can induce the immunogenic-cell death (ICD) of tumor cells and activate anti-tumor immune responses. However, it can also cause high expression of indole amine 2, 3-dioxygenase (IDO) during ICD, leading to T-cell apoptosis and a weakened immune response. An IDO inhibitor, 1-methyl tryptophan (1-MT), can inhibit the activity of IDO caused by MX, resulting in enhanced chemo-immunotherapy. Here, MX-1-MT was connected by ester bond which could be broken in an acidic tumor microenvironment. MX-1-MT was combined with polyethylene glycol (PEG) via a disulfide bond which could be reduced by glutathione overexpressed in tumors, thereby accelerating drug release at target sites. Folic acid-modified distearoyl phosphoethanolamine-polyethylene glycol (DSPE-PEG-FA) was introduced to form targeting micelles. The micelles were of uniform particle size, high stability, and high responsiveness. They could be taken-up by drug-resistant MCF-7/ADR cells, displayed high targeting ability, and induced enhanced cytotoxicity and ICD. Due to 1-MT addition, micelles could inhibit IDO. In vivo studies demonstrated that micelles could accumulate in the tumor tissues of nude mice, resulting in an enhanced antitumor effect and few side-effects.
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spelling pubmed-99702112023-02-28 Tumor microenvironment-responsive micelles assembled from a prodrug of mitoxantrone and 1-methyl tryptophan for enhanced chemo-immunotherapy Wang, Ru Li, Nuannuan Zhang, Tianyu Sun, Yiying He, Xiaoyan Lu, Xiaoyan Chu, Liuxiang Sun, Kaoxiang Drug Deliv Research Article Mitoxantrone (MX) can induce the immunogenic-cell death (ICD) of tumor cells and activate anti-tumor immune responses. However, it can also cause high expression of indole amine 2, 3-dioxygenase (IDO) during ICD, leading to T-cell apoptosis and a weakened immune response. An IDO inhibitor, 1-methyl tryptophan (1-MT), can inhibit the activity of IDO caused by MX, resulting in enhanced chemo-immunotherapy. Here, MX-1-MT was connected by ester bond which could be broken in an acidic tumor microenvironment. MX-1-MT was combined with polyethylene glycol (PEG) via a disulfide bond which could be reduced by glutathione overexpressed in tumors, thereby accelerating drug release at target sites. Folic acid-modified distearoyl phosphoethanolamine-polyethylene glycol (DSPE-PEG-FA) was introduced to form targeting micelles. The micelles were of uniform particle size, high stability, and high responsiveness. They could be taken-up by drug-resistant MCF-7/ADR cells, displayed high targeting ability, and induced enhanced cytotoxicity and ICD. Due to 1-MT addition, micelles could inhibit IDO. In vivo studies demonstrated that micelles could accumulate in the tumor tissues of nude mice, resulting in an enhanced antitumor effect and few side-effects. Taylor & Francis 2023-02-25 /pmc/articles/PMC9970211/ /pubmed/36840464 http://dx.doi.org/10.1080/10717544.2023.2182254 Text en © 2023 The Author(s). Published by Informa UK Limited, trading as Taylor & Francis Group. https://creativecommons.org/licenses/by-nc/4.0/This is an Open Access article distributed under the terms of the Creative Commons Attribution-NonCommercial License (http://creativecommons.org/licenses/by-nc/4.0/ (https://creativecommons.org/licenses/by-nc/4.0/) ), which permits unrestricted non-commercial use, distribution, and reproduction in any medium, provided the original work is properly cited.
spellingShingle Research Article
Wang, Ru
Li, Nuannuan
Zhang, Tianyu
Sun, Yiying
He, Xiaoyan
Lu, Xiaoyan
Chu, Liuxiang
Sun, Kaoxiang
Tumor microenvironment-responsive micelles assembled from a prodrug of mitoxantrone and 1-methyl tryptophan for enhanced chemo-immunotherapy
title Tumor microenvironment-responsive micelles assembled from a prodrug of mitoxantrone and 1-methyl tryptophan for enhanced chemo-immunotherapy
title_full Tumor microenvironment-responsive micelles assembled from a prodrug of mitoxantrone and 1-methyl tryptophan for enhanced chemo-immunotherapy
title_fullStr Tumor microenvironment-responsive micelles assembled from a prodrug of mitoxantrone and 1-methyl tryptophan for enhanced chemo-immunotherapy
title_full_unstemmed Tumor microenvironment-responsive micelles assembled from a prodrug of mitoxantrone and 1-methyl tryptophan for enhanced chemo-immunotherapy
title_short Tumor microenvironment-responsive micelles assembled from a prodrug of mitoxantrone and 1-methyl tryptophan for enhanced chemo-immunotherapy
title_sort tumor microenvironment-responsive micelles assembled from a prodrug of mitoxantrone and 1-methyl tryptophan for enhanced chemo-immunotherapy
topic Research Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9970211/
https://www.ncbi.nlm.nih.gov/pubmed/36840464
http://dx.doi.org/10.1080/10717544.2023.2182254
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