Enzymatically catalyzed molecular aggregation
Abstract The dynamic modulation of the aggregation process of small molecules represents an important research objective for scientists. However, the complex and dynamic nature of internal environments in vivo impedes controllable aggregation processes of single molecules. In this study, we successf...
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| Format: | Article |
| Language: | English |
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Nature Portfolio
2024-11-01
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| Series: | Nature Communications |
| Online Access: | https://doi.org/10.1038/s41467-024-54291-1 |
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| author | Wen-Jin Wang Rongyuan Zhang Liping Zhang Liang Hao Xu-Min Cai Qian Wu Zijie Qiu Ruijuan Han Jing Feng Shaojuan Wang Parvej Alam Guoqing Zhang Zheng Zhao Ben Zhong Tang |
| author_facet | Wen-Jin Wang Rongyuan Zhang Liping Zhang Liang Hao Xu-Min Cai Qian Wu Zijie Qiu Ruijuan Han Jing Feng Shaojuan Wang Parvej Alam Guoqing Zhang Zheng Zhao Ben Zhong Tang |
| author_sort | Wen-Jin Wang |
| collection | DOAJ |
| description | Abstract The dynamic modulation of the aggregation process of small molecules represents an important research objective for scientists. However, the complex and dynamic nature of internal environments in vivo impedes controllable aggregation processes of single molecules. In this study, we successfully achieve tumor-targeted aggregation of an aggregation-induced emission photosensitizer (AIE-PS), TBmA, with the catalysis of a tumor-overexpressed enzyme, γ-Glutamyl Transferase (GGT). Mechanistic investigations reveal that TBmA-Glu can be activated by GGT through cleavage of the γ-glutamyl bond and releasing TBmA. The poor water solubility of TBmA induces its aggregation, leading to aggregation-enhanced emission and photodynamic activities. The TBmA-Glu not only induces glutathione (GSH) depletion through GGT photo-degradation but also triggers lipid peroxidation accumulation and ferroptosis in cancer cells through photodynamic therapy. Finally, the in vivo studies conducted on female mice using both tumor xenograft and orthotopic liver cancer models have also demonstrated the significant anti-cancer effects of TBmA-Glu. The exceptional cancer-targeting ability and therapeutic efficiency demonstrated by this GGT activatable AIE-PS highlights enzymatic-mediated modulation as an effective approach for regulating small molecule aggregation intracellularly, thereby advancing innovative therapeutic strategies for various diseases. |
| format | Article |
| id | doaj-art-775dc46c7cb24035a9d30ef9f1795b2e |
| institution | Kabale University |
| issn | 2041-1723 |
| language | English |
| publishDate | 2024-11-01 |
| publisher | Nature Portfolio |
| record_format | Article |
| series | Nature Communications |
| spelling | doaj-art-775dc46c7cb24035a9d30ef9f1795b2e2024-11-24T12:34:02ZengNature PortfolioNature Communications2041-17232024-11-0115111110.1038/s41467-024-54291-1Enzymatically catalyzed molecular aggregationWen-Jin Wang0Rongyuan Zhang1Liping Zhang2Liang Hao3Xu-Min Cai4Qian Wu5Zijie Qiu6Ruijuan Han7Jing Feng8Shaojuan Wang9Parvej Alam10Guoqing Zhang11Zheng Zhao12Ben Zhong Tang13Clinical Translational Research Center of Aggregation-Induced Emission, The Second Affiliated Hospital, School of Medicine, The Chinese University of Hong Kong, Shenzhen (CUHK-Shenzhen)Clinical Translational Research Center of Aggregation-Induced Emission, The Second Affiliated Hospital, School of Medicine, The Chinese University of Hong Kong, Shenzhen (CUHK-Shenzhen)Clinical Translational Research Center of Aggregation-Induced Emission, The Second Affiliated Hospital, School of Medicine, The Chinese University of Hong Kong, Shenzhen (CUHK-Shenzhen)Clinical Translational Research Center of Aggregation-Induced Emission, The Second Affiliated Hospital, School of Medicine, The Chinese University of Hong Kong, Shenzhen (CUHK-Shenzhen)Jiangsu Co-Innovation Center of Efficient Processing and Utilization of Forest Resources, International Innovation Center for Forest Chemicals and Materials College of Chemical Engineering, Nanjing Forestry UniversityDepartment of Chemistry, The Hong Kong University of Science and Technology, Clear Water Bay, KowloonClinical Translational Research Center of Aggregation-Induced Emission, The Second Affiliated Hospital, School of Medicine, The Chinese University of Hong Kong, Shenzhen (CUHK-Shenzhen)Clinical Translational Research Center of Aggregation-Induced Emission, The Second Affiliated Hospital, School of Medicine, The Chinese University of Hong Kong, Shenzhen (CUHK-Shenzhen)Clinical Translational Research Center of Aggregation-Induced Emission, The Second Affiliated Hospital, School of Medicine, The Chinese University of Hong Kong, Shenzhen (CUHK-Shenzhen)Clinical Translational Research Center of Aggregation-Induced Emission, The Second Affiliated Hospital, School of Medicine, The Chinese University of Hong Kong, Shenzhen (CUHK-Shenzhen)Clinical Translational Research Center of Aggregation-Induced Emission, The Second Affiliated Hospital, School of Medicine, The Chinese University of Hong Kong, Shenzhen (CUHK-Shenzhen)University of Science and Technology of ChinaClinical Translational Research Center of Aggregation-Induced Emission, The Second Affiliated Hospital, School of Medicine, The Chinese University of Hong Kong, Shenzhen (CUHK-Shenzhen)Clinical Translational Research Center of Aggregation-Induced Emission, The Second Affiliated Hospital, School of Medicine, The Chinese University of Hong Kong, Shenzhen (CUHK-Shenzhen)Abstract The dynamic modulation of the aggregation process of small molecules represents an important research objective for scientists. However, the complex and dynamic nature of internal environments in vivo impedes controllable aggregation processes of single molecules. In this study, we successfully achieve tumor-targeted aggregation of an aggregation-induced emission photosensitizer (AIE-PS), TBmA, with the catalysis of a tumor-overexpressed enzyme, γ-Glutamyl Transferase (GGT). Mechanistic investigations reveal that TBmA-Glu can be activated by GGT through cleavage of the γ-glutamyl bond and releasing TBmA. The poor water solubility of TBmA induces its aggregation, leading to aggregation-enhanced emission and photodynamic activities. The TBmA-Glu not only induces glutathione (GSH) depletion through GGT photo-degradation but also triggers lipid peroxidation accumulation and ferroptosis in cancer cells through photodynamic therapy. Finally, the in vivo studies conducted on female mice using both tumor xenograft and orthotopic liver cancer models have also demonstrated the significant anti-cancer effects of TBmA-Glu. The exceptional cancer-targeting ability and therapeutic efficiency demonstrated by this GGT activatable AIE-PS highlights enzymatic-mediated modulation as an effective approach for regulating small molecule aggregation intracellularly, thereby advancing innovative therapeutic strategies for various diseases.https://doi.org/10.1038/s41467-024-54291-1 |
| spellingShingle | Wen-Jin Wang Rongyuan Zhang Liping Zhang Liang Hao Xu-Min Cai Qian Wu Zijie Qiu Ruijuan Han Jing Feng Shaojuan Wang Parvej Alam Guoqing Zhang Zheng Zhao Ben Zhong Tang Enzymatically catalyzed molecular aggregation Nature Communications |
| title | Enzymatically catalyzed molecular aggregation |
| title_full | Enzymatically catalyzed molecular aggregation |
| title_fullStr | Enzymatically catalyzed molecular aggregation |
| title_full_unstemmed | Enzymatically catalyzed molecular aggregation |
| title_short | Enzymatically catalyzed molecular aggregation |
| title_sort | enzymatically catalyzed molecular aggregation |
| url | https://doi.org/10.1038/s41467-024-54291-1 |
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