Engineered Extracellular Vesicles Driven by Erythrocytes Ameliorate Bacterial Sepsis by Iron Recycling, Toxin Clearing and Inflammation Regulation
Abstract Sepsis poses a significant challenge in clinical management. Effective strategies targeting iron restriction, toxin neutralization, and inflammation regulation are crucial in combating sepsis. However, a comprehensive approach simultaneously targeting these multiple processes has not been e...
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| Format: | Article |
| Language: | English |
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Wiley
2024-04-01
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| Series: | Advanced Science |
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| Online Access: | https://doi.org/10.1002/advs.202306884 |
| _version_ | 1797227544884281344 |
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| author | Yan Li Guanlin Qu Geng Dou Lili Ren Ming Dang Huijuan Kuang Lili Bao Feng Ding Guangzhou Xu Zhiyuan Zhang Chi Yang Shiyu Liu |
| author_facet | Yan Li Guanlin Qu Geng Dou Lili Ren Ming Dang Huijuan Kuang Lili Bao Feng Ding Guangzhou Xu Zhiyuan Zhang Chi Yang Shiyu Liu |
| author_sort | Yan Li |
| collection | DOAJ |
| description | Abstract Sepsis poses a significant challenge in clinical management. Effective strategies targeting iron restriction, toxin neutralization, and inflammation regulation are crucial in combating sepsis. However, a comprehensive approach simultaneously targeting these multiple processes has not been established. Here, an engineered apoptotic extracellular vesicles (apoEVs) derived from macrophages is developed and their potential as multifunctional agents for sepsis treatment is investigated. The extensive macrophage apoptosis in a Staphylococcus aureus‐induced sepsis model is discovered, unexpectedly revealing a protective role for the host. Mechanistically, the protective effects are mediated by apoptotic macrophage‐released apoEVs, which bound iron‐containing proteins and neutralized α‐toxin through interaction with membrane receptors (transferrin receptor and A disintegrin and metalloprotease 10). To further enhance therapeutic efficiency, apoEVs are engineered by incorporating mesoporous silica nanoparticles preloaded with anti‐inflammatory agents (microRNA‐146a). These engineered apoEVs can capture iron and neutralize α‐toxin with their natural membrane while also regulating inflammation by releasing microRNA‐146a in phagocytes. Moreover, to exploit the microcosmic movement and rotation capabilities, erythrocytes are utilized to drive the engineered apoEVs. The erythrocytes‐driven engineered apoEVs demonstrate a high capacity for toxin and iron capture, ultimately providing protection against sepsis associated with high iron‐loaded conditions. The findings establish a multifunctional agent that combines natural and engineered antibacterial strategies. |
| first_indexed | 2024-04-24T14:42:30Z |
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| institution | Directory Open Access Journal |
| issn | 2198-3844 |
| language | English |
| last_indexed | 2024-04-24T14:42:30Z |
| publishDate | 2024-04-01 |
| publisher | Wiley |
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| series | Advanced Science |
| spelling | doaj.art-27a66d6547384b1fb5d1e813a4fb6ca82024-04-02T20:51:56ZengWileyAdvanced Science2198-38442024-04-011113n/an/a10.1002/advs.202306884Engineered Extracellular Vesicles Driven by Erythrocytes Ameliorate Bacterial Sepsis by Iron Recycling, Toxin Clearing and Inflammation RegulationYan Li0Guanlin Qu1Geng Dou2Lili Ren3Ming Dang4Huijuan Kuang5Lili Bao6Feng Ding7Guangzhou Xu8Zhiyuan Zhang9Chi Yang10Shiyu Liu11National Center for Stomatology National Clinical Research Center for Oral Diseases Shanghai Key Laboratory of Stomatology Research Unit of Oral and Maxillofacial Regenerative Medicine Chinese Academy of Medical Sciences Department of Oral Surgery Shanghai Ninth People's Hospital Shanghai Jiao Tong University School of Medicine College of Stomatology Shanghai Jiao Tong University Shanghai 200011 ChinaNational Center for Stomatology National Clinical Research Center for Oral Diseases Shanghai Key Laboratory of Stomatology Research Unit of Oral and Maxillofacial Regenerative Medicine Chinese Academy of Medical Sciences Department of Oral Surgery Shanghai Ninth People's Hospital Shanghai Jiao Tong University School of Medicine College of Stomatology Shanghai Jiao Tong University Shanghai 200011 ChinaState Key Laboratory of Oral & Maxillofacial Reconstruction and Regeneration National Clinical Research Center for Oral Diseases Shaanxi International Joint Research Center for Oral Diseases Center for Tissue Engineering School of Stomatology The Fourth Military Medical University Shaanxi 710032 ChinaState Key Laboratory of Oral & Maxillofacial Reconstruction and Regeneration National Clinical Research Center for Oral Diseases Shaanxi International Joint Research Center for Oral Diseases Center for Tissue Engineering School of Stomatology The Fourth Military Medical University Shaanxi 710032 ChinaSchool of Dentistry University of Michigan Ann Arbor MI 48109 USAState Key Laboratory of Oral & Maxillofacial Reconstruction and Regeneration National Clinical Research Center for Oral Diseases Shaanxi International Joint Research Center for Oral Diseases Center for Tissue Engineering School of Stomatology The Fourth Military Medical University Shaanxi 710032 ChinaState Key Laboratory of Oral & Maxillofacial Reconstruction and Regeneration National Clinical Research Center for Oral Diseases Shaanxi International Joint Research Center for Oral Diseases Center for Tissue Engineering School of Stomatology The Fourth Military Medical University Shaanxi 710032 ChinaState Key Laboratory of Oral & Maxillofacial Reconstruction and Regeneration National Clinical Research Center for Oral Diseases Shaanxi International Joint Research Center for Oral Diseases Center for Tissue Engineering School of Stomatology The Fourth Military Medical University Shaanxi 710032 ChinaNational Center for Stomatology National Clinical Research Center for Oral Diseases Shanghai Key Laboratory of Stomatology Research Unit of Oral and Maxillofacial Regenerative Medicine Chinese Academy of Medical Sciences Department of Oral Surgery Shanghai Ninth People's Hospital Shanghai Jiao Tong University School of Medicine College of Stomatology Shanghai Jiao Tong University Shanghai 200011 ChinaNational Center for Stomatology National Clinical Research Center for Oral Diseases Shanghai Key Laboratory of Stomatology Research Unit of Oral and Maxillofacial Regenerative Medicine Chinese Academy of Medical Sciences Department of Oral Surgery Shanghai Ninth People's Hospital Shanghai Jiao Tong University School of Medicine College of Stomatology Shanghai Jiao Tong University Shanghai 200011 ChinaNational Center for Stomatology National Clinical Research Center for Oral Diseases Shanghai Key Laboratory of Stomatology Research Unit of Oral and Maxillofacial Regenerative Medicine Chinese Academy of Medical Sciences Department of Oral Surgery Shanghai Ninth People's Hospital Shanghai Jiao Tong University School of Medicine College of Stomatology Shanghai Jiao Tong University Shanghai 200011 ChinaState Key Laboratory of Oral & Maxillofacial Reconstruction and Regeneration National Clinical Research Center for Oral Diseases Shaanxi International Joint Research Center for Oral Diseases Center for Tissue Engineering School of Stomatology The Fourth Military Medical University Shaanxi 710032 ChinaAbstract Sepsis poses a significant challenge in clinical management. Effective strategies targeting iron restriction, toxin neutralization, and inflammation regulation are crucial in combating sepsis. However, a comprehensive approach simultaneously targeting these multiple processes has not been established. Here, an engineered apoptotic extracellular vesicles (apoEVs) derived from macrophages is developed and their potential as multifunctional agents for sepsis treatment is investigated. The extensive macrophage apoptosis in a Staphylococcus aureus‐induced sepsis model is discovered, unexpectedly revealing a protective role for the host. Mechanistically, the protective effects are mediated by apoptotic macrophage‐released apoEVs, which bound iron‐containing proteins and neutralized α‐toxin through interaction with membrane receptors (transferrin receptor and A disintegrin and metalloprotease 10). To further enhance therapeutic efficiency, apoEVs are engineered by incorporating mesoporous silica nanoparticles preloaded with anti‐inflammatory agents (microRNA‐146a). These engineered apoEVs can capture iron and neutralize α‐toxin with their natural membrane while also regulating inflammation by releasing microRNA‐146a in phagocytes. Moreover, to exploit the microcosmic movement and rotation capabilities, erythrocytes are utilized to drive the engineered apoEVs. The erythrocytes‐driven engineered apoEVs demonstrate a high capacity for toxin and iron capture, ultimately providing protection against sepsis associated with high iron‐loaded conditions. The findings establish a multifunctional agent that combines natural and engineered antibacterial strategies.https://doi.org/10.1002/advs.202306884bacterial infectionbioengineeringbiotechnologydrug deliveryextracellular vesicles |
| spellingShingle | Yan Li Guanlin Qu Geng Dou Lili Ren Ming Dang Huijuan Kuang Lili Bao Feng Ding Guangzhou Xu Zhiyuan Zhang Chi Yang Shiyu Liu Engineered Extracellular Vesicles Driven by Erythrocytes Ameliorate Bacterial Sepsis by Iron Recycling, Toxin Clearing and Inflammation Regulation Advanced Science bacterial infection bioengineering biotechnology drug delivery extracellular vesicles |
| title | Engineered Extracellular Vesicles Driven by Erythrocytes Ameliorate Bacterial Sepsis by Iron Recycling, Toxin Clearing and Inflammation Regulation |
| title_full | Engineered Extracellular Vesicles Driven by Erythrocytes Ameliorate Bacterial Sepsis by Iron Recycling, Toxin Clearing and Inflammation Regulation |
| title_fullStr | Engineered Extracellular Vesicles Driven by Erythrocytes Ameliorate Bacterial Sepsis by Iron Recycling, Toxin Clearing and Inflammation Regulation |
| title_full_unstemmed | Engineered Extracellular Vesicles Driven by Erythrocytes Ameliorate Bacterial Sepsis by Iron Recycling, Toxin Clearing and Inflammation Regulation |
| title_short | Engineered Extracellular Vesicles Driven by Erythrocytes Ameliorate Bacterial Sepsis by Iron Recycling, Toxin Clearing and Inflammation Regulation |
| title_sort | engineered extracellular vesicles driven by erythrocytes ameliorate bacterial sepsis by iron recycling toxin clearing and inflammation regulation |
| topic | bacterial infection bioengineering biotechnology drug delivery extracellular vesicles |
| url | https://doi.org/10.1002/advs.202306884 |
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