Nanomicelles for GLUT1-targeting hepatocellular carcinoma therapy based on NADPH depletion
AbstractHepatocellular carcinoma (HCC) is a malignant tumor leading cancer-associated high mortality worldwide. Unfortunately, the most commonly used drug therapeutics not only lack of target ability and efficiency, but also exhibit severe systemic toxicity to normal tissues. Thus, effective and tar...
| 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/10.1080/10717544.2022.2162160 |
| _version_ | 1797260988865576960 |
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| author | Congyi Zhang Zehui Liu Feng Wang Bin Zhang Xirui Zhang Peiwen Guo Tianwei Li Sheng Tai Changmei Zhang |
| author_facet | Congyi Zhang Zehui Liu Feng Wang Bin Zhang Xirui Zhang Peiwen Guo Tianwei Li Sheng Tai Changmei Zhang |
| author_sort | Congyi Zhang |
| collection | DOAJ |
| description | AbstractHepatocellular carcinoma (HCC) is a malignant tumor leading cancer-associated high mortality worldwide. Unfortunately, the most commonly used drug therapeutics not only lack of target ability and efficiency, but also exhibit severe systemic toxicity to normal tissues. Thus, effective and targeted nanodrug of HCC therapy is emerging as a more important issue. Here, we design and develop the novel nanomicelles, namely Mannose-polyethylene glycol 600-Nitroimidazole (Man-NIT). This micelle compound with high purity comprise two parts, which can self-assemble into nanoscale micelle. The outer shell is selected mannose as hydrophilic moiety, while the inner core is nitroimidazole as hydrophobic moiety. In the cell experiment, Man-NIT was more cellular uptake by HCCLM3 cells due to the mannose modification. Mannose as a kind of glucose transporter 1 (GLUT1) substrate, can specifically recognize and bind to over-expressed GLUT1 on carcinoma cytomembrane. The nitroimidazole moiety of Man-NIT was reduced by the over-expressed nitroreductase with reduced nicotinamide adenine dinucleotide phosphate (NADPH) as the cofactor, resulting in transient deletion of NADPH and glutathione (GSH). The increase of reactive oxygen species (ROS) in HCCLM3 cells disturbed the balance of redox, and finally caused the death of tumor cells. Additional in vivo experiment was conducted using twenty-four male BALB/c nude mice to build the tumor model. The results showed that nanomicelles were accumulated in the liver of mice. The tumor size and pathological features were obviously improved after nanomicelles treatment. It indicates that namomicelles have a tumor inhibition effect, especially Man-NIT, which may be a potential nanodrug of chemotherapeutics for HCC therapy. |
| first_indexed | 2024-03-08T23:31:56Z |
| format | Article |
| id | doaj.art-94972f68c2a748c1820686b73cb1836c |
| institution | Directory Open Access Journal |
| issn | 1071-7544 1521-0464 |
| language | English |
| last_indexed | 2024-04-24T23:34:04Z |
| publishDate | 2023-12-01 |
| publisher | Taylor & Francis Group |
| record_format | Article |
| series | Drug Delivery |
| spelling | doaj.art-94972f68c2a748c1820686b73cb1836c2024-03-15T14:22:17ZengTaylor & Francis GroupDrug Delivery1071-75441521-04642023-12-0130110.1080/10717544.2022.2162160Nanomicelles for GLUT1-targeting hepatocellular carcinoma therapy based on NADPH depletionCongyi Zhang0Zehui Liu1Feng Wang2Bin Zhang3Xirui Zhang4Peiwen Guo5Tianwei Li6Sheng Tai7Changmei Zhang8Department of Hepatic Surgery, Second Affiliated Hospital of Harbin Medical University, Harbin, ChinaDepartment of Children’s and Adolescent Health, Public Health College, Harbin Medical University, Harbin, ChinaDepartment of Children’s and Adolescent Health, Public Health College, Harbin Medical University, Harbin, ChinaDepartment of Hepatic Surgery, Second Affiliated Hospital of Harbin Medical University, Harbin, ChinaDepartment of Children’s and Adolescent Health, Public Health College, Harbin Medical University, Harbin, ChinaDepartment of Children’s and Adolescent Health, Public Health College, Harbin Medical University, Harbin, ChinaDepartment of Hepatic Surgery, Second Affiliated Hospital of Harbin Medical University, Harbin, ChinaDepartment of Hepatic Surgery, Second Affiliated Hospital of Harbin Medical University, Harbin, ChinaDepartment of Children’s and Adolescent Health, Public Health College, Harbin Medical University, Harbin, ChinaAbstractHepatocellular carcinoma (HCC) is a malignant tumor leading cancer-associated high mortality worldwide. Unfortunately, the most commonly used drug therapeutics not only lack of target ability and efficiency, but also exhibit severe systemic toxicity to normal tissues. Thus, effective and targeted nanodrug of HCC therapy is emerging as a more important issue. Here, we design and develop the novel nanomicelles, namely Mannose-polyethylene glycol 600-Nitroimidazole (Man-NIT). This micelle compound with high purity comprise two parts, which can self-assemble into nanoscale micelle. The outer shell is selected mannose as hydrophilic moiety, while the inner core is nitroimidazole as hydrophobic moiety. In the cell experiment, Man-NIT was more cellular uptake by HCCLM3 cells due to the mannose modification. Mannose as a kind of glucose transporter 1 (GLUT1) substrate, can specifically recognize and bind to over-expressed GLUT1 on carcinoma cytomembrane. The nitroimidazole moiety of Man-NIT was reduced by the over-expressed nitroreductase with reduced nicotinamide adenine dinucleotide phosphate (NADPH) as the cofactor, resulting in transient deletion of NADPH and glutathione (GSH). The increase of reactive oxygen species (ROS) in HCCLM3 cells disturbed the balance of redox, and finally caused the death of tumor cells. Additional in vivo experiment was conducted using twenty-four male BALB/c nude mice to build the tumor model. The results showed that nanomicelles were accumulated in the liver of mice. The tumor size and pathological features were obviously improved after nanomicelles treatment. It indicates that namomicelles have a tumor inhibition effect, especially Man-NIT, which may be a potential nanodrug of chemotherapeutics for HCC therapy.https://www.tandfonline.com/doi/10.1080/10717544.2022.2162160Hepatocellular carcinomananomicellesGLUT1-targetingNADPH depletion |
| spellingShingle | Congyi Zhang Zehui Liu Feng Wang Bin Zhang Xirui Zhang Peiwen Guo Tianwei Li Sheng Tai Changmei Zhang Nanomicelles for GLUT1-targeting hepatocellular carcinoma therapy based on NADPH depletion Drug Delivery Hepatocellular carcinoma nanomicelles GLUT1-targeting NADPH depletion |
| title | Nanomicelles for GLUT1-targeting hepatocellular carcinoma therapy based on NADPH depletion |
| title_full | Nanomicelles for GLUT1-targeting hepatocellular carcinoma therapy based on NADPH depletion |
| title_fullStr | Nanomicelles for GLUT1-targeting hepatocellular carcinoma therapy based on NADPH depletion |
| title_full_unstemmed | Nanomicelles for GLUT1-targeting hepatocellular carcinoma therapy based on NADPH depletion |
| title_short | Nanomicelles for GLUT1-targeting hepatocellular carcinoma therapy based on NADPH depletion |
| title_sort | nanomicelles for glut1 targeting hepatocellular carcinoma therapy based on nadph depletion |
| topic | Hepatocellular carcinoma nanomicelles GLUT1-targeting NADPH depletion |
| url | https://www.tandfonline.com/doi/10.1080/10717544.2022.2162160 |
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