Supramolecular Radiosensitizer Based on Hypoxia‐Responsive Macrocycle
Abstract Radiotherapy (RT) has been viewed as one of the most effective and extensively applied curatives in clinical cancer therapy. However, the radioresistance of tumor severely discounts the radiotherapy outcomes. Here, an innovative supramolecular radiotherapy strategy, based on the complexatio...
| Main Authors: | , , , , , , , , , , , |
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| Format: | Article |
| Language: | English |
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Wiley
2022-02-01
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| Series: | Advanced Science |
| Subjects: | |
| Online Access: | https://doi.org/10.1002/advs.202104349 |
| _version_ | 1819289963519279104 |
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| author | Xiaoxue Hou Yu‐Xuan Chang Yu‐Xin Yue Ze‐Han Wang Fei Ding Zhi‐Hao Li Hua‐Bin Li Yicheng Xu Xianglei Kong Fan Huang Dong‐Sheng Guo Jianfeng Liu |
| author_facet | Xiaoxue Hou Yu‐Xuan Chang Yu‐Xin Yue Ze‐Han Wang Fei Ding Zhi‐Hao Li Hua‐Bin Li Yicheng Xu Xianglei Kong Fan Huang Dong‐Sheng Guo Jianfeng Liu |
| author_sort | Xiaoxue Hou |
| collection | DOAJ |
| description | Abstract Radiotherapy (RT) has been viewed as one of the most effective and extensively applied curatives in clinical cancer therapy. However, the radioresistance of tumor severely discounts the radiotherapy outcomes. Here, an innovative supramolecular radiotherapy strategy, based on the complexation of a hypoxia‐responsive macrocycle with small‐molecule radiosensitizer, is reported. To exemplify this tactic, a carboxylated azocalix[4]arene (CAC4A) is devised as molecular container to quantitatively package tumor sensitizer banoxantrone dihydrochloride (AQ4N) through reversible host–guest interaction. Benefited from the selective reduction of azo functional groups under hypoxic microenvironment, the supramolecular prodrug CAC4A•AQ4N exhibits high tumor accumulation and efficient cellular internalization, thereby significantly amplifying radiation‐mediated tumor destruction without appreciable systemic toxicity. More importantly, this supramolecular radiotherapy strategy achieves an ultrahigh sensitizer enhancement ratio (SER) value of 2.349, which is the supreme among currently reported noncovalent‐based radiosensitization approach. Further development by applying different radiosensitizing drugs can make this supramolecular strategy become a general platform for boosting therapeutic effect in cancer radiotherapies, tremendously promising for clinical translation. |
| first_indexed | 2024-12-24T03:15:12Z |
| format | Article |
| id | doaj.art-8ac71cb8cd6c470699e6e70e78d81a75 |
| institution | Directory Open Access Journal |
| issn | 2198-3844 |
| language | English |
| last_indexed | 2024-12-24T03:15:12Z |
| publishDate | 2022-02-01 |
| publisher | Wiley |
| record_format | Article |
| series | Advanced Science |
| spelling | doaj.art-8ac71cb8cd6c470699e6e70e78d81a752022-12-21T17:17:40ZengWileyAdvanced Science2198-38442022-02-0196n/an/a10.1002/advs.202104349Supramolecular Radiosensitizer Based on Hypoxia‐Responsive MacrocycleXiaoxue Hou0Yu‐Xuan Chang1Yu‐Xin Yue2Ze‐Han Wang3Fei Ding4Zhi‐Hao Li5Hua‐Bin Li6Yicheng Xu7Xianglei Kong8Fan Huang9Dong‐Sheng Guo10Jianfeng Liu11CAMS Key Laboratory of Radiopharmacokinetics for Innovative Drugs Institute of Radiation Medicine Chinese Academy of Medical Sciences & Peking Union Medical College Tianjin 300192 P. R. ChinaCollege of Chemistry Key Laboratory of Functional Polymer Materials (Ministry of Education) State Key Laboratory of Elemento‐Organic Chemistry National Demonstration Center for Experimental Chemistry Education Nankai University Tianjin 300071 P. R. ChinaCollege of Chemistry Key Laboratory of Functional Polymer Materials (Ministry of Education) State Key Laboratory of Elemento‐Organic Chemistry National Demonstration Center for Experimental Chemistry Education Nankai University Tianjin 300071 P. R. ChinaCollege of Chemistry Key Laboratory of Functional Polymer Materials (Ministry of Education) State Key Laboratory of Elemento‐Organic Chemistry National Demonstration Center for Experimental Chemistry Education Nankai University Tianjin 300071 P. R. ChinaCollege of Chemistry Key Laboratory of Functional Polymer Materials (Ministry of Education) State Key Laboratory of Elemento‐Organic Chemistry National Demonstration Center for Experimental Chemistry Education Nankai University Tianjin 300071 P. R. ChinaCollege of Chemistry Key Laboratory of Functional Polymer Materials (Ministry of Education) State Key Laboratory of Elemento‐Organic Chemistry National Demonstration Center for Experimental Chemistry Education Nankai University Tianjin 300071 P. R. ChinaCollege of Chemistry Key Laboratory of Functional Polymer Materials (Ministry of Education) State Key Laboratory of Elemento‐Organic Chemistry National Demonstration Center for Experimental Chemistry Education Nankai University Tianjin 300071 P. R. ChinaCollege of Chemistry Key Laboratory of Functional Polymer Materials (Ministry of Education) State Key Laboratory of Elemento‐Organic Chemistry National Demonstration Center for Experimental Chemistry Education Nankai University Tianjin 300071 P. R. ChinaCollege of Chemistry Key Laboratory of Functional Polymer Materials (Ministry of Education) State Key Laboratory of Elemento‐Organic Chemistry National Demonstration Center for Experimental Chemistry Education Nankai University Tianjin 300071 P. R. ChinaCAMS Key Laboratory of Radiopharmacokinetics for Innovative Drugs Institute of Radiation Medicine Chinese Academy of Medical Sciences & Peking Union Medical College Tianjin 300192 P. R. ChinaCollege of Chemistry Key Laboratory of Functional Polymer Materials (Ministry of Education) State Key Laboratory of Elemento‐Organic Chemistry National Demonstration Center for Experimental Chemistry Education Nankai University Tianjin 300071 P. R. ChinaCAMS Key Laboratory of Radiopharmacokinetics for Innovative Drugs Institute of Radiation Medicine Chinese Academy of Medical Sciences & Peking Union Medical College Tianjin 300192 P. R. ChinaAbstract Radiotherapy (RT) has been viewed as one of the most effective and extensively applied curatives in clinical cancer therapy. However, the radioresistance of tumor severely discounts the radiotherapy outcomes. Here, an innovative supramolecular radiotherapy strategy, based on the complexation of a hypoxia‐responsive macrocycle with small‐molecule radiosensitizer, is reported. To exemplify this tactic, a carboxylated azocalix[4]arene (CAC4A) is devised as molecular container to quantitatively package tumor sensitizer banoxantrone dihydrochloride (AQ4N) through reversible host–guest interaction. Benefited from the selective reduction of azo functional groups under hypoxic microenvironment, the supramolecular prodrug CAC4A•AQ4N exhibits high tumor accumulation and efficient cellular internalization, thereby significantly amplifying radiation‐mediated tumor destruction without appreciable systemic toxicity. More importantly, this supramolecular radiotherapy strategy achieves an ultrahigh sensitizer enhancement ratio (SER) value of 2.349, which is the supreme among currently reported noncovalent‐based radiosensitization approach. Further development by applying different radiosensitizing drugs can make this supramolecular strategy become a general platform for boosting therapeutic effect in cancer radiotherapies, tremendously promising for clinical translation.https://doi.org/10.1002/advs.202104349calixarenedrug deliveryradiotherapysupramolecular chemistrytumor hypoxia |
| spellingShingle | Xiaoxue Hou Yu‐Xuan Chang Yu‐Xin Yue Ze‐Han Wang Fei Ding Zhi‐Hao Li Hua‐Bin Li Yicheng Xu Xianglei Kong Fan Huang Dong‐Sheng Guo Jianfeng Liu Supramolecular Radiosensitizer Based on Hypoxia‐Responsive Macrocycle Advanced Science calixarene drug delivery radiotherapy supramolecular chemistry tumor hypoxia |
| title | Supramolecular Radiosensitizer Based on Hypoxia‐Responsive Macrocycle |
| title_full | Supramolecular Radiosensitizer Based on Hypoxia‐Responsive Macrocycle |
| title_fullStr | Supramolecular Radiosensitizer Based on Hypoxia‐Responsive Macrocycle |
| title_full_unstemmed | Supramolecular Radiosensitizer Based on Hypoxia‐Responsive Macrocycle |
| title_short | Supramolecular Radiosensitizer Based on Hypoxia‐Responsive Macrocycle |
| title_sort | supramolecular radiosensitizer based on hypoxia responsive macrocycle |
| topic | calixarene drug delivery radiotherapy supramolecular chemistry tumor hypoxia |
| url | https://doi.org/10.1002/advs.202104349 |
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