Metformin and histone deacetylase inhibitor based anti-inflammatory nanoplatform for epithelial-mesenchymal transition suppression and metastatic tumor treatment
Abstract Epithelial-mesenchymal transition (EMT), a differentiation process with aberrant changes of tumor cells, is identified as an initial and vital procedure for metastatic processes. Inflammation is a significant inducer of EMT and provides an indispensable target for blocking EMT, however, an...
| Main Authors: | , , , , , , , , , |
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| Format: | Article |
| Language: | English |
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BMC
2022-08-01
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| Series: | Journal of Nanobiotechnology |
| Subjects: | |
| Online Access: | https://doi.org/10.1186/s12951-022-01592-6 |
| _version_ | 1798004298087399424 |
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| author | Tianze Jiang Laozhi Xie Songlei Zhou Yipu Liu Yukun Huang Ni Mei Fenfen Ma Jingru Gong Xiaoling Gao Jun Chen |
| author_facet | Tianze Jiang Laozhi Xie Songlei Zhou Yipu Liu Yukun Huang Ni Mei Fenfen Ma Jingru Gong Xiaoling Gao Jun Chen |
| author_sort | Tianze Jiang |
| collection | DOAJ |
| description | Abstract Epithelial-mesenchymal transition (EMT), a differentiation process with aberrant changes of tumor cells, is identified as an initial and vital procedure for metastatic processes. Inflammation is a significant inducer of EMT and provides an indispensable target for blocking EMT, however, an anti-inflammatory therapeutic with highlighted safety and efficacy is deficient. Metformin is a promising anti-inflammatory agent with low side effects, but tumor monotherapy with an anti-inflammation drug could generate therapy resistance, cell adaptation or even promote tumor development. Combination therapies with various anti-inflammatory mechanisms can be favorable options improving therapeutic effects of metformin, here we develop a tumor targeting hybrid micelle based on metformin and a histone deacetylase inhibitor propofol-docosahexaenoic acid for efficient therapeutic efficacies of anti-inflammatory drugs. Triptolide is further encapsulated in hybrid micelles for orthotopic tumor therapies. The final multifunctional nanoplatforms (HAOPTs) with hyaluronic acid (HA) modification can target tumor efficiently, inhibit tumor cell EMT processes, repress metastasis establishment and suppress metastatic tumor development in a synergistic manner. Collectively, the results afford proof of concept that the tumor targeting anti-inflammatory nanoplatform can provide a potent, safe and clinical translational approach for EMT inhibition and metastatic tumor therapy. |
| first_indexed | 2024-04-11T12:21:17Z |
| format | Article |
| id | doaj.art-46841363a93649cf837e25c7a48a8bb5 |
| institution | Directory Open Access Journal |
| issn | 1477-3155 |
| language | English |
| last_indexed | 2024-04-11T12:21:17Z |
| publishDate | 2022-08-01 |
| publisher | BMC |
| record_format | Article |
| series | Journal of Nanobiotechnology |
| spelling | doaj.art-46841363a93649cf837e25c7a48a8bb52022-12-22T04:24:05ZengBMCJournal of Nanobiotechnology1477-31552022-08-0120112110.1186/s12951-022-01592-6Metformin and histone deacetylase inhibitor based anti-inflammatory nanoplatform for epithelial-mesenchymal transition suppression and metastatic tumor treatmentTianze Jiang0Laozhi Xie1Songlei Zhou2Yipu Liu3Yukun Huang4Ni Mei5Fenfen Ma6Jingru Gong7Xiaoling Gao8Jun Chen9Shanghai Pudong Hospital & Department of Pharmaceutics, School of Pharmacy, Fudan UniversityShanghai Pudong Hospital & Department of Pharmaceutics, School of Pharmacy, Fudan UniversityShanghai Pudong Hospital & Department of Pharmaceutics, School of Pharmacy, Fudan UniversityShanghai Pudong Hospital & Department of Pharmaceutics, School of Pharmacy, Fudan UniversityShanghai Pudong Hospital & Department of Pharmaceutics, School of Pharmacy, Fudan UniversityShanghai Center for Drug Evaluation and InspectionShanghai Pudong Hospital & Department of Pharmaceutics, School of Pharmacy, Fudan UniversityShanghai Pudong Hospital & Department of Pharmaceutics, School of Pharmacy, Fudan UniversityDepartment of Pharmacology and Chemical Biology, Shanghai Jiao Tong University School of MedicineShanghai Pudong Hospital & Department of Pharmaceutics, School of Pharmacy, Fudan UniversityAbstract Epithelial-mesenchymal transition (EMT), a differentiation process with aberrant changes of tumor cells, is identified as an initial and vital procedure for metastatic processes. Inflammation is a significant inducer of EMT and provides an indispensable target for blocking EMT, however, an anti-inflammatory therapeutic with highlighted safety and efficacy is deficient. Metformin is a promising anti-inflammatory agent with low side effects, but tumor monotherapy with an anti-inflammation drug could generate therapy resistance, cell adaptation or even promote tumor development. Combination therapies with various anti-inflammatory mechanisms can be favorable options improving therapeutic effects of metformin, here we develop a tumor targeting hybrid micelle based on metformin and a histone deacetylase inhibitor propofol-docosahexaenoic acid for efficient therapeutic efficacies of anti-inflammatory drugs. Triptolide is further encapsulated in hybrid micelles for orthotopic tumor therapies. The final multifunctional nanoplatforms (HAOPTs) with hyaluronic acid (HA) modification can target tumor efficiently, inhibit tumor cell EMT processes, repress metastasis establishment and suppress metastatic tumor development in a synergistic manner. Collectively, the results afford proof of concept that the tumor targeting anti-inflammatory nanoplatform can provide a potent, safe and clinical translational approach for EMT inhibition and metastatic tumor therapy.https://doi.org/10.1186/s12951-022-01592-6Tumor metastasisAnti-inflammationEpithelial-mesenchymal transitionMetforminHistone deacetylase inhibitorNanoplatform |
| spellingShingle | Tianze Jiang Laozhi Xie Songlei Zhou Yipu Liu Yukun Huang Ni Mei Fenfen Ma Jingru Gong Xiaoling Gao Jun Chen Metformin and histone deacetylase inhibitor based anti-inflammatory nanoplatform for epithelial-mesenchymal transition suppression and metastatic tumor treatment Journal of Nanobiotechnology Tumor metastasis Anti-inflammation Epithelial-mesenchymal transition Metformin Histone deacetylase inhibitor Nanoplatform |
| title | Metformin and histone deacetylase inhibitor based anti-inflammatory nanoplatform for epithelial-mesenchymal transition suppression and metastatic tumor treatment |
| title_full | Metformin and histone deacetylase inhibitor based anti-inflammatory nanoplatform for epithelial-mesenchymal transition suppression and metastatic tumor treatment |
| title_fullStr | Metformin and histone deacetylase inhibitor based anti-inflammatory nanoplatform for epithelial-mesenchymal transition suppression and metastatic tumor treatment |
| title_full_unstemmed | Metformin and histone deacetylase inhibitor based anti-inflammatory nanoplatform for epithelial-mesenchymal transition suppression and metastatic tumor treatment |
| title_short | Metformin and histone deacetylase inhibitor based anti-inflammatory nanoplatform for epithelial-mesenchymal transition suppression and metastatic tumor treatment |
| title_sort | metformin and histone deacetylase inhibitor based anti inflammatory nanoplatform for epithelial mesenchymal transition suppression and metastatic tumor treatment |
| topic | Tumor metastasis Anti-inflammation Epithelial-mesenchymal transition Metformin Histone deacetylase inhibitor Nanoplatform |
| url | https://doi.org/10.1186/s12951-022-01592-6 |
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