Perylene‐Mediated Electron Leakage in Respiratory Chain to Trigger Endogenous ROS Burst for Hypoxic Cancer Chemo‐Immunotherapy
Abstract Perylene derivatives can be stimulated by the hypoxic tumor microenvironment to generate radical anion that is proposed to arouse electron exchange with oxidizing substance, and in turn, realize reactive oxygen species (ROS) burst. Here, three perylene therapeutic agents, PDI‐NI, PDIB‐NI, a...
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| Format: | Article |
| Language: | English |
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Wiley
2023-01-01
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| Series: | Advanced Science |
| Subjects: | |
| Online Access: | https://doi.org/10.1002/advs.202204498 |
| _version_ | 1797943406567096320 |
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| author | Bianbian Zhang Rijie Zheng Yuting Liu Xue Lou Wei Zhang Zhanjun Cui Yongwei Huang Tie Wang |
| author_facet | Bianbian Zhang Rijie Zheng Yuting Liu Xue Lou Wei Zhang Zhanjun Cui Yongwei Huang Tie Wang |
| author_sort | Bianbian Zhang |
| collection | DOAJ |
| description | Abstract Perylene derivatives can be stimulated by the hypoxic tumor microenvironment to generate radical anion that is proposed to arouse electron exchange with oxidizing substance, and in turn, realize reactive oxygen species (ROS) burst. Here, three perylene therapeutic agents, PDI‐NI, PDIB‐NI, and PDIC‐NI, are developed and it is found that the minimum lowest unoccupied molecular orbital (LUMO) energy level makes PDIC‐NI most easily accept electrons from the oxidative respiratory chain to form lots of anions, and the resultant maximum ROS generation, establishing an unambiguous mechanism for the formation of perylene radical anions in the cell, presents solid evidence for LUMO energy level determining endogenous ROS burst. Stirringly, PDIC‐NI‐induced ROS generation arouses enhanced mitochondrial oxidative stress and concurrently activates immunogenic cell death (ICD), which not only efficiently kills lung tumor cells but also reprograms immunosuppressive tumor microenvironment, including the cytokine secretion, dendritic cell maturation, as well as cytotoxic T lymphocytes activation, to inhibit the growth of xenografted and metastasis tumor, presenting a proof‐of‐concept demonstration of perylene that acts as an integrated therapeutic agent to well realize hypoxia‐activated chemotherapy with ICD‐induced immunotherapy on lung cancer. |
| first_indexed | 2024-04-10T20:23:39Z |
| format | Article |
| id | doaj.art-e47a1e7fc1e44b18b03345a24ea58e60 |
| institution | Directory Open Access Journal |
| issn | 2198-3844 |
| language | English |
| last_indexed | 2024-04-10T20:23:39Z |
| publishDate | 2023-01-01 |
| publisher | Wiley |
| record_format | Article |
| series | Advanced Science |
| spelling | doaj.art-e47a1e7fc1e44b18b03345a24ea58e602023-01-25T13:47:50ZengWileyAdvanced Science2198-38442023-01-01103n/an/a10.1002/advs.202204498Perylene‐Mediated Electron Leakage in Respiratory Chain to Trigger Endogenous ROS Burst for Hypoxic Cancer Chemo‐ImmunotherapyBianbian Zhang0Rijie Zheng1Yuting Liu2Xue Lou3Wei Zhang4Zhanjun Cui5Yongwei Huang6Tie Wang7Laboratory for NanoMedical Photonics School of Basic Medical Science Henan University Kaifeng 475004 P. R. ChinaLaboratory for NanoMedical Photonics School of Basic Medical Science Henan University Kaifeng 475004 P. R. ChinaLaboratory for NanoMedical Photonics School of Basic Medical Science Henan University Kaifeng 475004 P. R. ChinaLaboratory for NanoMedical Photonics School of Basic Medical Science Henan University Kaifeng 475004 P. R. ChinaTianjin Key Laboratory of Drug Targeting and Bioimaging Life and Health Intelligent Research Institute Tianjin University of Technology Tianjin 300384 P. R. ChinaLaboratory for NanoMedical Photonics School of Basic Medical Science Henan University Kaifeng 475004 P. R. ChinaLaboratory for NanoMedical Photonics School of Basic Medical Science Henan University Kaifeng 475004 P. R. ChinaTianjin Key Laboratory of Drug Targeting and Bioimaging Life and Health Intelligent Research Institute Tianjin University of Technology Tianjin 300384 P. R. ChinaAbstract Perylene derivatives can be stimulated by the hypoxic tumor microenvironment to generate radical anion that is proposed to arouse electron exchange with oxidizing substance, and in turn, realize reactive oxygen species (ROS) burst. Here, three perylene therapeutic agents, PDI‐NI, PDIB‐NI, and PDIC‐NI, are developed and it is found that the minimum lowest unoccupied molecular orbital (LUMO) energy level makes PDIC‐NI most easily accept electrons from the oxidative respiratory chain to form lots of anions, and the resultant maximum ROS generation, establishing an unambiguous mechanism for the formation of perylene radical anions in the cell, presents solid evidence for LUMO energy level determining endogenous ROS burst. Stirringly, PDIC‐NI‐induced ROS generation arouses enhanced mitochondrial oxidative stress and concurrently activates immunogenic cell death (ICD), which not only efficiently kills lung tumor cells but also reprograms immunosuppressive tumor microenvironment, including the cytokine secretion, dendritic cell maturation, as well as cytotoxic T lymphocytes activation, to inhibit the growth of xenografted and metastasis tumor, presenting a proof‐of‐concept demonstration of perylene that acts as an integrated therapeutic agent to well realize hypoxia‐activated chemotherapy with ICD‐induced immunotherapy on lung cancer.https://doi.org/10.1002/advs.202204498chemo‐immunotherapyendogenous reactive oxygen species bursthypoxic tumorimmunogenic cell deathperylene |
| spellingShingle | Bianbian Zhang Rijie Zheng Yuting Liu Xue Lou Wei Zhang Zhanjun Cui Yongwei Huang Tie Wang Perylene‐Mediated Electron Leakage in Respiratory Chain to Trigger Endogenous ROS Burst for Hypoxic Cancer Chemo‐Immunotherapy Advanced Science chemo‐immunotherapy endogenous reactive oxygen species burst hypoxic tumor immunogenic cell death perylene |
| title | Perylene‐Mediated Electron Leakage in Respiratory Chain to Trigger Endogenous ROS Burst for Hypoxic Cancer Chemo‐Immunotherapy |
| title_full | Perylene‐Mediated Electron Leakage in Respiratory Chain to Trigger Endogenous ROS Burst for Hypoxic Cancer Chemo‐Immunotherapy |
| title_fullStr | Perylene‐Mediated Electron Leakage in Respiratory Chain to Trigger Endogenous ROS Burst for Hypoxic Cancer Chemo‐Immunotherapy |
| title_full_unstemmed | Perylene‐Mediated Electron Leakage in Respiratory Chain to Trigger Endogenous ROS Burst for Hypoxic Cancer Chemo‐Immunotherapy |
| title_short | Perylene‐Mediated Electron Leakage in Respiratory Chain to Trigger Endogenous ROS Burst for Hypoxic Cancer Chemo‐Immunotherapy |
| title_sort | perylene mediated electron leakage in respiratory chain to trigger endogenous ros burst for hypoxic cancer chemo immunotherapy |
| topic | chemo‐immunotherapy endogenous reactive oxygen species burst hypoxic tumor immunogenic cell death perylene |
| url | https://doi.org/10.1002/advs.202204498 |
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