Ruthenium(II) Lipid‐Mimics Drive Lipid Phase Separation to Arouse Autophagy‐Ferroptosis Cascade for Photoimmunotherapy
Abstract Lipid‐mediated phase separation is crucial for the formation of lipophilic spontaneous domain to regulate lipid metabolism and homeostasis, furtherly contributing to multiple cell death pathways. Herein, a series of Ru(II) lipid‐mimics based on short chains or midchain lipids are developed....
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Wiley
2025-01-01
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| Series: | Advanced Science |
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| Online Access: | https://doi.org/10.1002/advs.202411629 |
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| author | Yue Zheng Wen‐Jin Wang Jing‐Xin Chen Kun Peng Xiao‐Xiao Chen Qing‐Hua Shen Bing‐Bing Liang Zong‐Wan Mao Cai‐Ping Tan |
| author_facet | Yue Zheng Wen‐Jin Wang Jing‐Xin Chen Kun Peng Xiao‐Xiao Chen Qing‐Hua Shen Bing‐Bing Liang Zong‐Wan Mao Cai‐Ping Tan |
| author_sort | Yue Zheng |
| collection | DOAJ |
| description | Abstract Lipid‐mediated phase separation is crucial for the formation of lipophilic spontaneous domain to regulate lipid metabolism and homeostasis, furtherly contributing to multiple cell death pathways. Herein, a series of Ru(II) lipid‐mimics based on short chains or midchain lipids are developed. Among them, Ru‐LipM with two dodecyl chains significantly induces natural lipid phase separation via hydrocarbon chain‐melting phase transitions. Accompanied by the aggregation of Ru‐LipM‐labeled lipophilic membrane‐less compartments, most polyunsaturated lipids are increased and the autophagic flux is retarded with the adaptor protein sequestosome 1 (p62). Upon low‐dose irradiation, Ru‐LipM further drives ferritinophagy, providing an additional source of labile iron and rendering cells more sensitive to ferroptosis. Meanwhile, the peroxidation of polyunsaturated lipids occurs due to the deactivation of glutathione peroxidase 4 (GPX4) and the overexpression of acyl‐CoA synthetase long‐chain family member 4 (ACSL4), leading to the immunogenic ferroptosis. Ultimately, both innate and adaptive immunity are invigorated, indicating the tremendous antitumor capability of Ru‐LipM in vivo. This study presents an unprecedented discovery of small molecules capable of inducing and monitoring lipid phase separation, thereby eliciting robust immune responses in living cells. It provides a biosimulation strategy for constructing efficient metal‐based immune activators. |
| format | Article |
| id | doaj-art-d192b6442ba043c5a529182e87579367 |
| institution | Kabale University |
| issn | 2198-3844 |
| language | English |
| publishDate | 2025-01-01 |
| publisher | Wiley |
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| series | Advanced Science |
| spelling | doaj-art-d192b6442ba043c5a529182e875793672025-01-20T13:04:18ZengWileyAdvanced Science2198-38442025-01-01123n/an/a10.1002/advs.202411629Ruthenium(II) Lipid‐Mimics Drive Lipid Phase Separation to Arouse Autophagy‐Ferroptosis Cascade for PhotoimmunotherapyYue Zheng0Wen‐Jin Wang1Jing‐Xin Chen2Kun Peng3Xiao‐Xiao Chen4Qing‐Hua Shen5Bing‐Bing Liang6Zong‐Wan Mao7Cai‐Ping Tan8MOE Key Laboratory of Bioinorganic and Synthetic Chemistry, State Key Laboratory of Anti‐Infective Drug Development, IGCME, GBRCE for Functional Molecular Engineering, School of Chemistry Sun Yat‐Sen University Guangzhou 510006 P. R. ChinaMOE Key Laboratory of Bioinorganic and Synthetic Chemistry, State Key Laboratory of Anti‐Infective Drug Development, IGCME, GBRCE for Functional Molecular Engineering, School of Chemistry Sun Yat‐Sen University Guangzhou 510006 P. R. ChinaMOE Key Laboratory of Bioinorganic and Synthetic Chemistry, State Key Laboratory of Anti‐Infective Drug Development, IGCME, GBRCE for Functional Molecular Engineering, School of Chemistry Sun Yat‐Sen University Guangzhou 510006 P. R. ChinaMOE Key Laboratory of Bioinorganic and Synthetic Chemistry, State Key Laboratory of Anti‐Infective Drug Development, IGCME, GBRCE for Functional Molecular Engineering, School of Chemistry Sun Yat‐Sen University Guangzhou 510006 P. R. ChinaMOE Key Laboratory of Bioinorganic and Synthetic Chemistry, State Key Laboratory of Anti‐Infective Drug Development, IGCME, GBRCE for Functional Molecular Engineering, School of Chemistry Sun Yat‐Sen University Guangzhou 510006 P. R. ChinaMOE Key Laboratory of Bioinorganic and Synthetic Chemistry, State Key Laboratory of Anti‐Infective Drug Development, IGCME, GBRCE for Functional Molecular Engineering, School of Chemistry Sun Yat‐Sen University Guangzhou 510006 P. R. ChinaMOE Key Laboratory of Bioinorganic and Synthetic Chemistry, State Key Laboratory of Anti‐Infective Drug Development, IGCME, GBRCE for Functional Molecular Engineering, School of Chemistry Sun Yat‐Sen University Guangzhou 510006 P. R. ChinaMOE Key Laboratory of Bioinorganic and Synthetic Chemistry, State Key Laboratory of Anti‐Infective Drug Development, IGCME, GBRCE for Functional Molecular Engineering, School of Chemistry Sun Yat‐Sen University Guangzhou 510006 P. R. ChinaMOE Key Laboratory of Bioinorganic and Synthetic Chemistry, State Key Laboratory of Anti‐Infective Drug Development, IGCME, GBRCE for Functional Molecular Engineering, School of Chemistry Sun Yat‐Sen University Guangzhou 510006 P. R. ChinaAbstract Lipid‐mediated phase separation is crucial for the formation of lipophilic spontaneous domain to regulate lipid metabolism and homeostasis, furtherly contributing to multiple cell death pathways. Herein, a series of Ru(II) lipid‐mimics based on short chains or midchain lipids are developed. Among them, Ru‐LipM with two dodecyl chains significantly induces natural lipid phase separation via hydrocarbon chain‐melting phase transitions. Accompanied by the aggregation of Ru‐LipM‐labeled lipophilic membrane‐less compartments, most polyunsaturated lipids are increased and the autophagic flux is retarded with the adaptor protein sequestosome 1 (p62). Upon low‐dose irradiation, Ru‐LipM further drives ferritinophagy, providing an additional source of labile iron and rendering cells more sensitive to ferroptosis. Meanwhile, the peroxidation of polyunsaturated lipids occurs due to the deactivation of glutathione peroxidase 4 (GPX4) and the overexpression of acyl‐CoA synthetase long‐chain family member 4 (ACSL4), leading to the immunogenic ferroptosis. Ultimately, both innate and adaptive immunity are invigorated, indicating the tremendous antitumor capability of Ru‐LipM in vivo. This study presents an unprecedented discovery of small molecules capable of inducing and monitoring lipid phase separation, thereby eliciting robust immune responses in living cells. It provides a biosimulation strategy for constructing efficient metal‐based immune activators.https://doi.org/10.1002/advs.202411629autophagyferroptosislipid phase separationphotoimmunotherapyruthenium complexes |
| spellingShingle | Yue Zheng Wen‐Jin Wang Jing‐Xin Chen Kun Peng Xiao‐Xiao Chen Qing‐Hua Shen Bing‐Bing Liang Zong‐Wan Mao Cai‐Ping Tan Ruthenium(II) Lipid‐Mimics Drive Lipid Phase Separation to Arouse Autophagy‐Ferroptosis Cascade for Photoimmunotherapy Advanced Science autophagy ferroptosis lipid phase separation photoimmunotherapy ruthenium complexes |
| title | Ruthenium(II) Lipid‐Mimics Drive Lipid Phase Separation to Arouse Autophagy‐Ferroptosis Cascade for Photoimmunotherapy |
| title_full | Ruthenium(II) Lipid‐Mimics Drive Lipid Phase Separation to Arouse Autophagy‐Ferroptosis Cascade for Photoimmunotherapy |
| title_fullStr | Ruthenium(II) Lipid‐Mimics Drive Lipid Phase Separation to Arouse Autophagy‐Ferroptosis Cascade for Photoimmunotherapy |
| title_full_unstemmed | Ruthenium(II) Lipid‐Mimics Drive Lipid Phase Separation to Arouse Autophagy‐Ferroptosis Cascade for Photoimmunotherapy |
| title_short | Ruthenium(II) Lipid‐Mimics Drive Lipid Phase Separation to Arouse Autophagy‐Ferroptosis Cascade for Photoimmunotherapy |
| title_sort | ruthenium ii lipid mimics drive lipid phase separation to arouse autophagy ferroptosis cascade for photoimmunotherapy |
| topic | autophagy ferroptosis lipid phase separation photoimmunotherapy ruthenium complexes |
| url | https://doi.org/10.1002/advs.202411629 |
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