Engineered Bacterial Outer Membrane Vesicles Hitchhiking on Neutrophils for Antibody Drug Delivery to Enhance Postoperative Immune Checkpoint Therapy
Abstract In clinical practice, surgical removal of tumors often leaves behind small tumors and circulating tumor cells, increasing the risk of metastasis and recurrence, which seriously affects treatment outcomes. Immunotherapy activates the immune system to monitor and inhibit tumor metastasis and...
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| Language: | English |
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Wiley
2025-07-01
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| Series: | Advanced Science |
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| Online Access: | https://doi.org/10.1002/advs.202505000 |
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| author | Meng Guan Xiao‐Ting Xie Dong Zhou Kai Cheng Bin Zhang Xin‐Yue Xu Yong Li Yi‐Tong Zhou Wei Peng Li‐Li Chen Peng‐Shuo Dong Si Chen Jia‐Hua Zou Bo Liu Yuan‐Di Zhao Jin‐Xuan Fan |
| author_facet | Meng Guan Xiao‐Ting Xie Dong Zhou Kai Cheng Bin Zhang Xin‐Yue Xu Yong Li Yi‐Tong Zhou Wei Peng Li‐Li Chen Peng‐Shuo Dong Si Chen Jia‐Hua Zou Bo Liu Yuan‐Di Zhao Jin‐Xuan Fan |
| author_sort | Meng Guan |
| collection | DOAJ |
| description | Abstract In clinical practice, surgical removal of tumors often leaves behind small tumors and circulating tumor cells, increasing the risk of metastasis and recurrence, which seriously affects treatment outcomes. Immunotherapy activates the immune system to monitor and inhibit tumor metastasis and recurrence long‐term. However, inflammatory microenvironments at surgical sites lead to immunosuppressive tumor‐associated macrophages (TAMs), causing immune evasion. Additionally, tumor cells overexpress the immune checkpoint CD47, further weakening the phagocytic and cytotoxic functions of macrophages. Here, the bacterial outer membrane vesicles (OMV) hitchhiking on neutrophils are utilized to precisely deliver immune checkpoint blockade antibodies to the tumor resection site. Escherichia coli is reprogrammed to express CD47 antibody and used to extract CD47 antibody‐containing OMV, followed by insertion of Ce6 photosensitizer into the membrane (OC47‐Ce6). Purified autologous neutrophils phagocytose and carry OC47‐Ce6 for precise targeting to the postoperative tumor resection site, mediating tumor cell killing, aCD47 release, and tumor‐associated antigen presentation by light. In vitro and in vivo experiments demonstrate that OC47‐Ce6 enhances TAM phagocytic function through TAM polarization and CD47 blockade. This approach effectively activates T‐cell anti‐tumor immune responses and significantly reduces the risk of postoperative tumor recurrence and metastasis. |
| format | Article |
| id | doaj-art-3f312aa0c29f445f9247bbe6efd4f85a |
| institution | Kabale University |
| issn | 2198-3844 |
| language | English |
| publishDate | 2025-07-01 |
| publisher | Wiley |
| record_format | Article |
| series | Advanced Science |
| spelling | doaj-art-3f312aa0c29f445f9247bbe6efd4f85a2025-08-20T03:50:58ZengWileyAdvanced Science2198-38442025-07-011227n/an/a10.1002/advs.202505000Engineered Bacterial Outer Membrane Vesicles Hitchhiking on Neutrophils for Antibody Drug Delivery to Enhance Postoperative Immune Checkpoint TherapyMeng Guan0Xiao‐Ting Xie1Dong Zhou2Kai Cheng3Bin Zhang4Xin‐Yue Xu5Yong Li6Yi‐Tong Zhou7Wei Peng8Li‐Li Chen9Peng‐Shuo Dong10Si Chen11Jia‐Hua Zou12Bo Liu13Yuan‐Di Zhao14Jin‐Xuan Fan15Britton Chance Center for Biomedical Photonics at Wuhan National Laboratory for Optoelectronics – Hubei Bioinformatics & Molecular Imaging Key Laboratory Department of Biomedical Engineering College of Life Science and Technology Huazhong University of Science and Technology Wuhan Hubei 430074 P. R. ChinaBritton Chance Center for Biomedical Photonics at Wuhan National Laboratory for Optoelectronics – Hubei Bioinformatics & Molecular Imaging Key Laboratory Department of Biomedical Engineering College of Life Science and Technology Huazhong University of Science and Technology Wuhan Hubei 430074 P. R. ChinaDepartment of Oncology Huanggang Central Hospital of Yangtze University Huanggang Hubei 438000 P. R. ChinaBritton Chance Center for Biomedical Photonics at Wuhan National Laboratory for Optoelectronics – Hubei Bioinformatics & Molecular Imaging Key Laboratory Department of Biomedical Engineering College of Life Science and Technology Huazhong University of Science and Technology Wuhan Hubei 430074 P. R. ChinaBritton Chance Center for Biomedical Photonics at Wuhan National Laboratory for Optoelectronics – Hubei Bioinformatics & Molecular Imaging Key Laboratory Department of Biomedical Engineering College of Life Science and Technology Huazhong University of Science and Technology Wuhan Hubei 430074 P. R. ChinaBritton Chance Center for Biomedical Photonics at Wuhan National Laboratory for Optoelectronics – Hubei Bioinformatics & Molecular Imaging Key Laboratory Department of Biomedical Engineering College of Life Science and Technology Huazhong University of Science and Technology Wuhan Hubei 430074 P. R. ChinaBritton Chance Center for Biomedical Photonics at Wuhan National Laboratory for Optoelectronics – Hubei Bioinformatics & Molecular Imaging Key Laboratory Department of Biomedical Engineering College of Life Science and Technology Huazhong University of Science and Technology Wuhan Hubei 430074 P. R. ChinaBritton Chance Center for Biomedical Photonics at Wuhan National Laboratory for Optoelectronics – Hubei Bioinformatics & Molecular Imaging Key Laboratory Department of Biomedical Engineering College of Life Science and Technology Huazhong University of Science and Technology Wuhan Hubei 430074 P. R. ChinaHubei Clinical Medical Research Center of Esophageal and Gastric Malignancy Huanggang Hubei 438021 P.R. ChinaBritton Chance Center for Biomedical Photonics at Wuhan National Laboratory for Optoelectronics – Hubei Bioinformatics & Molecular Imaging Key Laboratory Department of Biomedical Engineering College of Life Science and Technology Huazhong University of Science and Technology Wuhan Hubei 430074 P. R. ChinaBritton Chance Center for Biomedical Photonics at Wuhan National Laboratory for Optoelectronics – Hubei Bioinformatics & Molecular Imaging Key Laboratory Department of Biomedical Engineering College of Life Science and Technology Huazhong University of Science and Technology Wuhan Hubei 430074 P. R. ChinaHubei Key Laboratory of Plasma Chemistry and Advanced Materials School of Material Science and Engineering Wuhan Institute of Technology Wuhan Hubei 430205 P. R. ChinaBritton Chance Center for Biomedical Photonics at Wuhan National Laboratory for Optoelectronics – Hubei Bioinformatics & Molecular Imaging Key Laboratory Department of Biomedical Engineering College of Life Science and Technology Huazhong University of Science and Technology Wuhan Hubei 430074 P. R. ChinaBritton Chance Center for Biomedical Photonics at Wuhan National Laboratory for Optoelectronics – Hubei Bioinformatics & Molecular Imaging Key Laboratory Department of Biomedical Engineering College of Life Science and Technology Huazhong University of Science and Technology Wuhan Hubei 430074 P. R. ChinaBritton Chance Center for Biomedical Photonics at Wuhan National Laboratory for Optoelectronics – Hubei Bioinformatics & Molecular Imaging Key Laboratory Department of Biomedical Engineering College of Life Science and Technology Huazhong University of Science and Technology Wuhan Hubei 430074 P. R. ChinaBritton Chance Center for Biomedical Photonics at Wuhan National Laboratory for Optoelectronics – Hubei Bioinformatics & Molecular Imaging Key Laboratory Department of Biomedical Engineering College of Life Science and Technology Huazhong University of Science and Technology Wuhan Hubei 430074 P. R. ChinaAbstract In clinical practice, surgical removal of tumors often leaves behind small tumors and circulating tumor cells, increasing the risk of metastasis and recurrence, which seriously affects treatment outcomes. Immunotherapy activates the immune system to monitor and inhibit tumor metastasis and recurrence long‐term. However, inflammatory microenvironments at surgical sites lead to immunosuppressive tumor‐associated macrophages (TAMs), causing immune evasion. Additionally, tumor cells overexpress the immune checkpoint CD47, further weakening the phagocytic and cytotoxic functions of macrophages. Here, the bacterial outer membrane vesicles (OMV) hitchhiking on neutrophils are utilized to precisely deliver immune checkpoint blockade antibodies to the tumor resection site. Escherichia coli is reprogrammed to express CD47 antibody and used to extract CD47 antibody‐containing OMV, followed by insertion of Ce6 photosensitizer into the membrane (OC47‐Ce6). Purified autologous neutrophils phagocytose and carry OC47‐Ce6 for precise targeting to the postoperative tumor resection site, mediating tumor cell killing, aCD47 release, and tumor‐associated antigen presentation by light. In vitro and in vivo experiments demonstrate that OC47‐Ce6 enhances TAM phagocytic function through TAM polarization and CD47 blockade. This approach effectively activates T‐cell anti‐tumor immune responses and significantly reduces the risk of postoperative tumor recurrence and metastasis.https://doi.org/10.1002/advs.202505000engineered bacteriaimmunotherapyneutrophilsouter membrane vesicles |
| spellingShingle | Meng Guan Xiao‐Ting Xie Dong Zhou Kai Cheng Bin Zhang Xin‐Yue Xu Yong Li Yi‐Tong Zhou Wei Peng Li‐Li Chen Peng‐Shuo Dong Si Chen Jia‐Hua Zou Bo Liu Yuan‐Di Zhao Jin‐Xuan Fan Engineered Bacterial Outer Membrane Vesicles Hitchhiking on Neutrophils for Antibody Drug Delivery to Enhance Postoperative Immune Checkpoint Therapy Advanced Science engineered bacteria immunotherapy neutrophils outer membrane vesicles |
| title | Engineered Bacterial Outer Membrane Vesicles Hitchhiking on Neutrophils for Antibody Drug Delivery to Enhance Postoperative Immune Checkpoint Therapy |
| title_full | Engineered Bacterial Outer Membrane Vesicles Hitchhiking on Neutrophils for Antibody Drug Delivery to Enhance Postoperative Immune Checkpoint Therapy |
| title_fullStr | Engineered Bacterial Outer Membrane Vesicles Hitchhiking on Neutrophils for Antibody Drug Delivery to Enhance Postoperative Immune Checkpoint Therapy |
| title_full_unstemmed | Engineered Bacterial Outer Membrane Vesicles Hitchhiking on Neutrophils for Antibody Drug Delivery to Enhance Postoperative Immune Checkpoint Therapy |
| title_short | Engineered Bacterial Outer Membrane Vesicles Hitchhiking on Neutrophils for Antibody Drug Delivery to Enhance Postoperative Immune Checkpoint Therapy |
| title_sort | engineered bacterial outer membrane vesicles hitchhiking on neutrophils for antibody drug delivery to enhance postoperative immune checkpoint therapy |
| topic | engineered bacteria immunotherapy neutrophils outer membrane vesicles |
| url | https://doi.org/10.1002/advs.202505000 |
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