Dual hypoxia-responsive supramolecular complex for cancer target therapy
Abstract The prognosis with pancreatic cancer is among the poorest of any human cancer. One of the important factors is the tumor hypoxia. Targeting tumor hypoxia is considered a desirable therapeutic option. However, it has not been translated into clinical success in the treatment of pancreatic ca...
| Main Authors: | , , , , , , , , , , , , |
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| Format: | Article |
| Language: | English |
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Nature Portfolio
2023-09-01
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| Series: | Nature Communications |
| Online Access: | https://doi.org/10.1038/s41467-023-41388-2 |
| _version_ | 1797558562250031104 |
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| author | Jian-Shuang Guo Juan-Juan Li Ze-Han Wang Yang Liu Yu-Xin Yue Hua-Bin Li Xiu-He Zhao Yuan-Jun Sun Ya-Hui Ding Fei Ding Dong-Sheng Guo Liang Wang Yue Chen |
| author_facet | Jian-Shuang Guo Juan-Juan Li Ze-Han Wang Yang Liu Yu-Xin Yue Hua-Bin Li Xiu-He Zhao Yuan-Jun Sun Ya-Hui Ding Fei Ding Dong-Sheng Guo Liang Wang Yue Chen |
| author_sort | Jian-Shuang Guo |
| collection | DOAJ |
| description | Abstract The prognosis with pancreatic cancer is among the poorest of any human cancer. One of the important factors is the tumor hypoxia. Targeting tumor hypoxia is considered a desirable therapeutic option. However, it has not been translated into clinical success in the treatment of pancreatic cancer. With enhanced cytotoxicities against hypoxic pancreatic cancer cells, BE-43547A2 (BE) may serve as a promising template for hypoxia target strategy. Here, based on rational modification, a BE prodrug (NMP-BE) is encapsulated into sulfonated azocalix[5]arene (SAC5A) to generate a supramolecular dual hypoxia-responsive complex NMP-BE@SAC5A. Benefited from the selective load release within cancer cells, NMP-BE@SAC5A markedly suppresses tumor growth at low dose in pancreatic cancer cells xenograft murine model without developing systemic toxicity. This research presents a strategy for the modification of covalent compounds to achieve efficient delivery within tumors, a horizon for the realization of safe and reinforced hypoxia target therapy using a simple approach. |
| first_indexed | 2024-03-10T17:33:12Z |
| format | Article |
| id | doaj.art-03ab6172e76143cc9bbbf4daa81fcc60 |
| institution | Directory Open Access Journal |
| issn | 2041-1723 |
| language | English |
| last_indexed | 2024-03-10T17:33:12Z |
| publishDate | 2023-09-01 |
| publisher | Nature Portfolio |
| record_format | Article |
| series | Nature Communications |
| spelling | doaj.art-03ab6172e76143cc9bbbf4daa81fcc602023-11-20T09:56:06ZengNature PortfolioNature Communications2041-17232023-09-0114111310.1038/s41467-023-41388-2Dual hypoxia-responsive supramolecular complex for cancer target therapyJian-Shuang Guo0Juan-Juan Li1Ze-Han Wang2Yang Liu3Yu-Xin Yue4Hua-Bin Li5Xiu-He Zhao6Yuan-Jun Sun7Ya-Hui Ding8Fei Ding9Dong-Sheng Guo10Liang Wang11Yue Chen12College of Pharmacy, State Key Laboratory of Medicinal Chemical Biology, Tianjin Key Laboratory of Molecular Drug Research, Nankai UniversityCollege of Chemistry, State Key Laboratory of Elemento-Organic Chemistry, Key Laboratory of Functional Polymer Materials (Ministry of Education), Nankai UniversityCollege of Chemistry, State Key Laboratory of Elemento-Organic Chemistry, Key Laboratory of Functional Polymer Materials (Ministry of Education), Nankai UniversityCollege of Pharmacy, State Key Laboratory of Medicinal Chemical Biology, Tianjin Key Laboratory of Molecular Drug Research, Nankai UniversityCollege of Chemistry, State Key Laboratory of Elemento-Organic Chemistry, Key Laboratory of Functional Polymer Materials (Ministry of Education), Nankai UniversityCollege of Chemistry, State Key Laboratory of Elemento-Organic Chemistry, Key Laboratory of Functional Polymer Materials (Ministry of Education), Nankai UniversityCollege of Pharmacy, State Key Laboratory of Medicinal Chemical Biology, Tianjin Key Laboratory of Molecular Drug Research, Nankai UniversityCollege of Pharmacy, State Key Laboratory of Medicinal Chemical Biology, Tianjin Key Laboratory of Molecular Drug Research, Nankai UniversityCollege of Chemistry, State Key Laboratory of Medicinal Chemical Biology, Nankai UniversityCollege of Chemistry, State Key Laboratory of Elemento-Organic Chemistry, Key Laboratory of Functional Polymer Materials (Ministry of Education), Nankai UniversityCollege of Chemistry, State Key Laboratory of Elemento-Organic Chemistry, Key Laboratory of Functional Polymer Materials (Ministry of Education), Nankai UniversityCollege of Chemistry, State Key Laboratory of Medicinal Chemical Biology, Nankai UniversityCollege of Chemistry, State Key Laboratory of Medicinal Chemical Biology, Nankai UniversityAbstract The prognosis with pancreatic cancer is among the poorest of any human cancer. One of the important factors is the tumor hypoxia. Targeting tumor hypoxia is considered a desirable therapeutic option. However, it has not been translated into clinical success in the treatment of pancreatic cancer. With enhanced cytotoxicities against hypoxic pancreatic cancer cells, BE-43547A2 (BE) may serve as a promising template for hypoxia target strategy. Here, based on rational modification, a BE prodrug (NMP-BE) is encapsulated into sulfonated azocalix[5]arene (SAC5A) to generate a supramolecular dual hypoxia-responsive complex NMP-BE@SAC5A. Benefited from the selective load release within cancer cells, NMP-BE@SAC5A markedly suppresses tumor growth at low dose in pancreatic cancer cells xenograft murine model without developing systemic toxicity. This research presents a strategy for the modification of covalent compounds to achieve efficient delivery within tumors, a horizon for the realization of safe and reinforced hypoxia target therapy using a simple approach.https://doi.org/10.1038/s41467-023-41388-2 |
| spellingShingle | Jian-Shuang Guo Juan-Juan Li Ze-Han Wang Yang Liu Yu-Xin Yue Hua-Bin Li Xiu-He Zhao Yuan-Jun Sun Ya-Hui Ding Fei Ding Dong-Sheng Guo Liang Wang Yue Chen Dual hypoxia-responsive supramolecular complex for cancer target therapy Nature Communications |
| title | Dual hypoxia-responsive supramolecular complex for cancer target therapy |
| title_full | Dual hypoxia-responsive supramolecular complex for cancer target therapy |
| title_fullStr | Dual hypoxia-responsive supramolecular complex for cancer target therapy |
| title_full_unstemmed | Dual hypoxia-responsive supramolecular complex for cancer target therapy |
| title_short | Dual hypoxia-responsive supramolecular complex for cancer target therapy |
| title_sort | dual hypoxia responsive supramolecular complex for cancer target therapy |
| url | https://doi.org/10.1038/s41467-023-41388-2 |
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