Supramolecular Detoxification Approach of Endotoxin Through Host–Guest Complexation by a Giant Macrocycle
In Gram-negative bacteria, lipopolysaccharides (LPSs, also known as endotoxin) can induce extensive immune responses that will enable victims to produce severe septic shock syndrome. Because of the high mortality of sepsis in the face of standard treatment, advance detoxification schemes are urgentl...
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| Format: | Article |
| Language: | English |
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MDPI AG
2025-07-01
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| Series: | Molecules |
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| Online Access: | https://www.mdpi.com/1420-3049/30/15/3188 |
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| author | Junyi Chen Xiang Yu Shujie Lin Zihan Fang Shenghui Li Liguo Xie Zhibing Zheng Qingbin Meng |
| author_facet | Junyi Chen Xiang Yu Shujie Lin Zihan Fang Shenghui Li Liguo Xie Zhibing Zheng Qingbin Meng |
| author_sort | Junyi Chen |
| collection | DOAJ |
| description | In Gram-negative bacteria, lipopolysaccharides (LPSs, also known as endotoxin) can induce extensive immune responses that will enable victims to produce severe septic shock syndrome. Because of the high mortality of sepsis in the face of standard treatment, advance detoxification schemes are urgently needed in clinics. Herein, we described a supramolecular detoxification approach via direct host–guest complexation by a giant macrocycle. Cationic pentaphen[3]arene (CPP3) bearing multiple quaternary ammonium groups was screened as a candidate antidote. CPP3 exhibited robust binding affinity toward LPS with an association constant of (4.79 ± 0.29) × 10<sup>8</sup> M<sup>−1</sup>. Co-dosing with an equivalent amount of CPP3 has been demonstrated to decrease LPS-induced cytotoxicity on a cellular level through inhibiting ROS generation and proinflammatory cytokine expression. In vivo experiments have further proved that post-treatment by CPP3 could significantly improve the survival rate of LPS-poisoned mice from 0 to 100% over a period of 3 days, and inflammatory abnormalities and tissue damage were also alleviated. |
| format | Article |
| id | doaj-art-3ee965733cad473ca452ab683fc8af14 |
| institution | Kabale University |
| issn | 1420-3049 |
| language | English |
| publishDate | 2025-07-01 |
| publisher | MDPI AG |
| record_format | Article |
| series | Molecules |
| spelling | doaj-art-3ee965733cad473ca452ab683fc8af142025-08-20T03:36:41ZengMDPI AGMolecules1420-30492025-07-013015318810.3390/molecules30153188Supramolecular Detoxification Approach of Endotoxin Through Host–Guest Complexation by a Giant MacrocycleJunyi Chen0Xiang Yu1Shujie Lin2Zihan Fang3Shenghui Li4Liguo Xie5Zhibing Zheng6Qingbin Meng7Academy of Military Medical Sciences, Beijing 100850, ChinaAcademy of Military Medical Sciences, Beijing 100850, ChinaAcademy of Military Medical Sciences, Beijing 100850, ChinaAcademy of Military Medical Sciences, Beijing 100850, ChinaAcademy of Military Medical Sciences, Beijing 100850, ChinaAcademy of Military Medical Sciences, Beijing 100850, ChinaAcademy of Military Medical Sciences, Beijing 100850, ChinaAcademy of Military Medical Sciences, Beijing 100850, ChinaIn Gram-negative bacteria, lipopolysaccharides (LPSs, also known as endotoxin) can induce extensive immune responses that will enable victims to produce severe septic shock syndrome. Because of the high mortality of sepsis in the face of standard treatment, advance detoxification schemes are urgently needed in clinics. Herein, we described a supramolecular detoxification approach via direct host–guest complexation by a giant macrocycle. Cationic pentaphen[3]arene (CPP3) bearing multiple quaternary ammonium groups was screened as a candidate antidote. CPP3 exhibited robust binding affinity toward LPS with an association constant of (4.79 ± 0.29) × 10<sup>8</sup> M<sup>−1</sup>. Co-dosing with an equivalent amount of CPP3 has been demonstrated to decrease LPS-induced cytotoxicity on a cellular level through inhibiting ROS generation and proinflammatory cytokine expression. In vivo experiments have further proved that post-treatment by CPP3 could significantly improve the survival rate of LPS-poisoned mice from 0 to 100% over a period of 3 days, and inflammatory abnormalities and tissue damage were also alleviated.https://www.mdpi.com/1420-3049/30/15/3188endotoxinmacrocyclehost–guest complexationsupramolecular detoxification approach |
| spellingShingle | Junyi Chen Xiang Yu Shujie Lin Zihan Fang Shenghui Li Liguo Xie Zhibing Zheng Qingbin Meng Supramolecular Detoxification Approach of Endotoxin Through Host–Guest Complexation by a Giant Macrocycle Molecules endotoxin macrocycle host–guest complexation supramolecular detoxification approach |
| title | Supramolecular Detoxification Approach of Endotoxin Through Host–Guest Complexation by a Giant Macrocycle |
| title_full | Supramolecular Detoxification Approach of Endotoxin Through Host–Guest Complexation by a Giant Macrocycle |
| title_fullStr | Supramolecular Detoxification Approach of Endotoxin Through Host–Guest Complexation by a Giant Macrocycle |
| title_full_unstemmed | Supramolecular Detoxification Approach of Endotoxin Through Host–Guest Complexation by a Giant Macrocycle |
| title_short | Supramolecular Detoxification Approach of Endotoxin Through Host–Guest Complexation by a Giant Macrocycle |
| title_sort | supramolecular detoxification approach of endotoxin through host guest complexation by a giant macrocycle |
| topic | endotoxin macrocycle host–guest complexation supramolecular detoxification approach |
| url | https://www.mdpi.com/1420-3049/30/15/3188 |
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