Tumor microenvironment-responsive micelles assembled from a prodrug of mitoxantrone and 1-methyl tryptophan for enhanced chemo-immunotherapy
AbstractMitoxantrone (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...
| Main Authors: | , , , , , , , |
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| Format: | Article |
| Language: | English |
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Taylor & Francis Group
2023-12-01
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| Series: | Drug Delivery |
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| Online Access: | https://www.tandfonline.com/doi/10.1080/10717544.2023.2182254 |
| _version_ | 1797260980777910272 |
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| author | Ru Wang Nuannuan Li Tianyu Zhang Yiying Sun Xiaoyan He Xiaoyan Lu Liuxiang Chu Kaoxiang Sun |
| author_facet | Ru Wang Nuannuan Li Tianyu Zhang Yiying Sun Xiaoyan He Xiaoyan Lu Liuxiang Chu Kaoxiang Sun |
| author_sort | Ru Wang |
| collection | DOAJ |
| description | AbstractMitoxantrone (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. |
| first_indexed | 2024-03-08T23:31:29Z |
| format | Article |
| id | doaj.art-2fb7697ded2b4d45b98cd7482ceb1b6d |
| institution | Directory Open Access Journal |
| issn | 1071-7544 1521-0464 |
| language | English |
| last_indexed | 2024-04-24T23:33:57Z |
| publishDate | 2023-12-01 |
| publisher | Taylor & Francis Group |
| record_format | Article |
| series | Drug Delivery |
| spelling | doaj.art-2fb7697ded2b4d45b98cd7482ceb1b6d2024-03-15T14:22:17ZengTaylor & Francis GroupDrug Delivery1071-75441521-04642023-12-0130110.1080/10717544.2023.2182254Tumor microenvironment-responsive micelles assembled from a prodrug of mitoxantrone and 1-methyl tryptophan for enhanced chemo-immunotherapyRu Wang0Nuannuan Li1Tianyu Zhang2Yiying Sun3Xiaoyan He4Xiaoyan Lu5Liuxiang Chu6Kaoxiang Sun7Key Laboratory of Molecular Pharmacology and Drug Evaluation (Yantai University), School of Pharmacy, Collaborative Innovation Center of Advanced Drug Delivery System and Biotech Drugs in Universities of Shandong, Ministry of Education, Yantai University, Yantai, Shandong Province, ChinaKey Laboratory of Molecular Pharmacology and Drug Evaluation (Yantai University), School of Pharmacy, Collaborative Innovation Center of Advanced Drug Delivery System and Biotech Drugs in Universities of Shandong, Ministry of Education, Yantai University, Yantai, Shandong Province, ChinaKey Laboratory of Molecular Pharmacology and Drug Evaluation (Yantai University), School of Pharmacy, Collaborative Innovation Center of Advanced Drug Delivery System and Biotech Drugs in Universities of Shandong, Ministry of Education, Yantai University, Yantai, Shandong Province, ChinaYantai Saipute Analyzing Service Co. Ltd, Yantai, Shandong Province, ChinaKey Laboratory of Molecular Pharmacology and Drug Evaluation (Yantai University), School of Pharmacy, Collaborative Innovation Center of Advanced Drug Delivery System and Biotech Drugs in Universities of Shandong, Ministry of Education, Yantai University, Yantai, Shandong Province, ChinaKey Laboratory of Molecular Pharmacology and Drug Evaluation (Yantai University), School of Pharmacy, Collaborative Innovation Center of Advanced Drug Delivery System and Biotech Drugs in Universities of Shandong, Ministry of Education, Yantai University, Yantai, Shandong Province, ChinaKey Laboratory of Molecular Pharmacology and Drug Evaluation (Yantai University), School of Pharmacy, Collaborative Innovation Center of Advanced Drug Delivery System and Biotech Drugs in Universities of Shandong, Ministry of Education, Yantai University, Yantai, Shandong Province, ChinaKey Laboratory of Molecular Pharmacology and Drug Evaluation (Yantai University), School of Pharmacy, Collaborative Innovation Center of Advanced Drug Delivery System and Biotech Drugs in Universities of Shandong, Ministry of Education, Yantai University, Yantai, Shandong Province, ChinaAbstractMitoxantrone (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.https://www.tandfonline.com/doi/10.1080/10717544.2023.2182254Mitoxantronechemo-immunotherapydisulfide bondactive targetingmicellesmultidrug resistance |
| spellingShingle | Ru Wang Nuannuan Li Tianyu Zhang Yiying Sun Xiaoyan He Xiaoyan Lu Liuxiang Chu Kaoxiang Sun Tumor microenvironment-responsive micelles assembled from a prodrug of mitoxantrone and 1-methyl tryptophan for enhanced chemo-immunotherapy Drug Delivery Mitoxantrone chemo-immunotherapy disulfide bond active targeting micelles multidrug resistance |
| 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 | Mitoxantrone chemo-immunotherapy disulfide bond active targeting micelles multidrug resistance |
| url | https://www.tandfonline.com/doi/10.1080/10717544.2023.2182254 |
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