Neutrophil‐Mimicking Nanomedicine Eliminates Tumor Intracellular Bacteria and Enhances Chemotherapy on Liver Metastasis of Colorectal Cancer
Abstract Fusobacterium nucleatum (Fn) enrichment has been identified in colorectal cancer and its liver metastases. In this study, we found that Fn predominantly accumulated within colorectal cancer cells, correlating with colorectal cancer liver metastasis. Clinically, the administration of high do...
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| Format: | Article |
| Language: | English |
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Wiley
2025-08-01
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| Series: | Advanced Science |
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| Online Access: | https://doi.org/10.1002/advs.202504188 |
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| author | Yanan Niu Xu Zhao Yong Li Xiaoya Ma Weifeng Yang Jie Ma Wanglin Li Wei Yuan |
| author_facet | Yanan Niu Xu Zhao Yong Li Xiaoya Ma Weifeng Yang Jie Ma Wanglin Li Wei Yuan |
| author_sort | Yanan Niu |
| collection | DOAJ |
| description | Abstract Fusobacterium nucleatum (Fn) enrichment has been identified in colorectal cancer and its liver metastases. In this study, we found that Fn predominantly accumulated within colorectal cancer cells, correlating with colorectal cancer liver metastasis. Clinically, the administration of high doses of antibiotics and chemotherapeutic agents can disrupt the balance of the host microbiota. To address this clinical challenge, metronidazole (MTI) and oxaliplatin (OXA) are encapsulated within poly (lactic‐co‐glycolic acid) (PLGA) nanoparticles. Neutrophil membrane vesicles are extracted from murine bone marrow and coated with these nanoparticles (NM@PLGA‐MTI‐OXA), creating neutrophil‐mimetic nanoparticles with dual targeting capabilities for antibacterial and anticancer purposes. The neutrophil membrane coating, compared with free drugs, is found to enhance nanoparticle uptake by tumor cells, facilitating intracellular bacterial elimination and tumor cell death. Further experiments reveal that NM@PLGA‐MTI‐OXA reverses the Fn‐induced epithelial‐mesenchymal transition (EMT) in tumor cells during metastasis and remodels the immunosuppressive microenvironment, suppressing colorectal cancer and liver metastasis development while minimizing broad‐spectrum damage to the commensal microbiota. |
| format | Article |
| id | doaj-art-0830878024aa4909bed1fa6e613274a4 |
| institution | Kabale University |
| issn | 2198-3844 |
| language | English |
| publishDate | 2025-08-01 |
| publisher | Wiley |
| record_format | Article |
| series | Advanced Science |
| spelling | doaj-art-0830878024aa4909bed1fa6e613274a42025-08-20T11:56:10ZengWileyAdvanced Science2198-38442025-08-011230n/an/a10.1002/advs.202504188Neutrophil‐Mimicking Nanomedicine Eliminates Tumor Intracellular Bacteria and Enhances Chemotherapy on Liver Metastasis of Colorectal CancerYanan Niu0Xu Zhao1Yong Li2Xiaoya Ma3Weifeng Yang4Jie Ma5Wanglin Li6Wei Yuan7State Key Laboratory of Molecular Oncology National Cancer Center/Cancer Hospital Chinese Academy of Medical Sciences Peking Union Medical College Beijing 100021 P. R. ChinaState Key Laboratory of Molecular Oncology National Cancer Center/Cancer Hospital Chinese Academy of Medical Sciences Peking Union Medical College Beijing 100021 P. R. ChinaDepartment of Thoracic Surgery National Cancer Center/Cancer Hospital Chinese Academy of Medical Sciences Peking Union Medical College Beijing 100021 P. R. ChinaState Key Laboratory of Molecular Oncology National Cancer Center/Cancer Hospital Chinese Academy of Medical Sciences Peking Union Medical College Beijing 100021 P. R. ChinaDepartment of Gastrointestinal Surgery Huadu District Peoples' Hospital of Guangzhou 48 Xinhua Road, Huadu District Guangzhou 510800 P. R. ChinaDepartment of Biotherapy Beijing Hospital National Center of Gerontology Institute of Geriatric Medicine Chinese Academy of Medical Sciences Graduate School of Peking Union Medical College Beijing 100730 P. R. ChinaDepartment of Gastrointestinal Surgery Huadu District Peoples' Hospital of Guangzhou 48 Xinhua Road, Huadu District Guangzhou 510800 P. R. ChinaState Key Laboratory of Molecular Oncology National Cancer Center/Cancer Hospital Chinese Academy of Medical Sciences Peking Union Medical College Beijing 100021 P. R. ChinaAbstract Fusobacterium nucleatum (Fn) enrichment has been identified in colorectal cancer and its liver metastases. In this study, we found that Fn predominantly accumulated within colorectal cancer cells, correlating with colorectal cancer liver metastasis. Clinically, the administration of high doses of antibiotics and chemotherapeutic agents can disrupt the balance of the host microbiota. To address this clinical challenge, metronidazole (MTI) and oxaliplatin (OXA) are encapsulated within poly (lactic‐co‐glycolic acid) (PLGA) nanoparticles. Neutrophil membrane vesicles are extracted from murine bone marrow and coated with these nanoparticles (NM@PLGA‐MTI‐OXA), creating neutrophil‐mimetic nanoparticles with dual targeting capabilities for antibacterial and anticancer purposes. The neutrophil membrane coating, compared with free drugs, is found to enhance nanoparticle uptake by tumor cells, facilitating intracellular bacterial elimination and tumor cell death. Further experiments reveal that NM@PLGA‐MTI‐OXA reverses the Fn‐induced epithelial‐mesenchymal transition (EMT) in tumor cells during metastasis and remodels the immunosuppressive microenvironment, suppressing colorectal cancer and liver metastasis development while minimizing broad‐spectrum damage to the commensal microbiota.https://doi.org/10.1002/advs.202504188colorectal cancerliver metastasisnanomedicinetumor microbiome |
| spellingShingle | Yanan Niu Xu Zhao Yong Li Xiaoya Ma Weifeng Yang Jie Ma Wanglin Li Wei Yuan Neutrophil‐Mimicking Nanomedicine Eliminates Tumor Intracellular Bacteria and Enhances Chemotherapy on Liver Metastasis of Colorectal Cancer Advanced Science colorectal cancer liver metastasis nanomedicine tumor microbiome |
| title | Neutrophil‐Mimicking Nanomedicine Eliminates Tumor Intracellular Bacteria and Enhances Chemotherapy on Liver Metastasis of Colorectal Cancer |
| title_full | Neutrophil‐Mimicking Nanomedicine Eliminates Tumor Intracellular Bacteria and Enhances Chemotherapy on Liver Metastasis of Colorectal Cancer |
| title_fullStr | Neutrophil‐Mimicking Nanomedicine Eliminates Tumor Intracellular Bacteria and Enhances Chemotherapy on Liver Metastasis of Colorectal Cancer |
| title_full_unstemmed | Neutrophil‐Mimicking Nanomedicine Eliminates Tumor Intracellular Bacteria and Enhances Chemotherapy on Liver Metastasis of Colorectal Cancer |
| title_short | Neutrophil‐Mimicking Nanomedicine Eliminates Tumor Intracellular Bacteria and Enhances Chemotherapy on Liver Metastasis of Colorectal Cancer |
| title_sort | neutrophil mimicking nanomedicine eliminates tumor intracellular bacteria and enhances chemotherapy on liver metastasis of colorectal cancer |
| topic | colorectal cancer liver metastasis nanomedicine tumor microbiome |
| url | https://doi.org/10.1002/advs.202504188 |
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