Homologous targeted neutrophils-liposome system for pyroptosis-enhanced antitumor immunotherapy of triple-negative breast cancer
Triple-negative breast cancer (TNBC), characterized by negative expression of estrogen receptor, progesterone receptor, and oncogene HER-2, always exhibits resistance to targeted drugs. Immunotherapies have demonstrated promising clinical responses and significant potential for TNBC treatment. Enhan...
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Elsevier
2025-06-01
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| Series: | Materials Today Bio |
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| Online Access: | http://www.sciencedirect.com/science/article/pii/S2590006425004740 |
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| author | Ge Gao Xiaodi Xu Xiaoyang Liu Yao-Wen Jiang Meng Wang Tong Su Jiaxuan Chen Mingxia Xue Weixiang Zhong Yuxin Chen Peng Jiang Junnian Zheng Gang Wang |
| author_facet | Ge Gao Xiaodi Xu Xiaoyang Liu Yao-Wen Jiang Meng Wang Tong Su Jiaxuan Chen Mingxia Xue Weixiang Zhong Yuxin Chen Peng Jiang Junnian Zheng Gang Wang |
| author_sort | Ge Gao |
| collection | DOAJ |
| description | Triple-negative breast cancer (TNBC), characterized by negative expression of estrogen receptor, progesterone receptor, and oncogene HER-2, always exhibits resistance to targeted drugs. Immunotherapies have demonstrated promising clinical responses and significant potential for TNBC treatment. Enhancing and activating antitumoral immunity can help restrain TNBC progression. In this work, we developed and validated an irradiation-responsive, tumor-targeting, and pyroptosis-enhanced drug delivery system based on neutrophils for effective TNBC treatment. Specifically, TNBC cell membrane-derived liposomes were loaded with photothermal agent IR775 and a pyroptosis-promoting plasmid carrying GSDME coding sequence (GI-LNPs). These GI-LNPs were then anchored onto the surface of neutrophils via biotin-avidin interaction and delivered into the tumor through local injury-driven neutrophil infiltration. Compared to conventional therapeutic strategies, NE-GI-LNPs accumulated and penetrated more deeply into tumor tissues. Furthermore, IR775-triggered the generation of caspase-3 under NIR laser irradiation promoted the cleavage of expressed GSDME, converting apoptosis to pyroptosis in 4T1 cells and enhancing antitumor immunity. Overall, our study demonstrated that multifunctional GI-LNPs delivered by neutrophils could effectively inhibit tumor growth through pyroptosis-enhanced antitumor immunotherapy. |
| format | Article |
| id | doaj-art-986f0aee2c5d48edaeff6287d0b3f455 |
| institution | OA Journals |
| issn | 2590-0064 |
| language | English |
| publishDate | 2025-06-01 |
| publisher | Elsevier |
| record_format | Article |
| series | Materials Today Bio |
| spelling | doaj-art-986f0aee2c5d48edaeff6287d0b3f4552025-08-20T02:29:20ZengElsevierMaterials Today Bio2590-00642025-06-013210190410.1016/j.mtbio.2025.101904Homologous targeted neutrophils-liposome system for pyroptosis-enhanced antitumor immunotherapy of triple-negative breast cancerGe Gao0Xiaodi Xu1Xiaoyang Liu2Yao-Wen Jiang3Meng Wang4Tong Su5Jiaxuan Chen6Mingxia Xue7Weixiang Zhong8Yuxin Chen9Peng Jiang10Junnian Zheng11Gang Wang12Cancer Institute, Xuzhou Medical University, 209 Tongshan Road, Xuzhou, Jiangsu, 221004, China; Center of Clinical Oncology, The Affiliated Hospital of Xuzhou Medical University, 99 Huaihai Road, Xuzhou, Jiangsu, 221002, China; Jiangsu Center for the Collaboration and Innovation of Cancer Biotherapy, Xuzhou Medical University, 209 Tongshan Road, Xuzhou, Jiangsu, 221004, China; Corresponding author. Cancer Institute, Xuzhou Medical University, 209 Tongshan Road, Xuzhou, Jiangsu, 221004, China.Cancer Institute, Xuzhou Medical University, 209 Tongshan Road, Xuzhou, Jiangsu, 221004, China; Center of Clinical Oncology, The Affiliated Hospital of Xuzhou Medical University, 99 Huaihai Road, Xuzhou, Jiangsu, 221002, China; Jiangsu Center for the Collaboration and Innovation of Cancer Biotherapy, Xuzhou Medical University, 209 Tongshan Road, Xuzhou, Jiangsu, 221004, ChinaState Key Laboratory of Bioelectronics, School of Biological Science and Medical Engineering, Southeast University, Nanjing, Jiangsu, 210096, ChinaSchool of Medical Imaging, Xuzhou Medical University, 209 Tongshan Road, Xuzhou, Jiangsu, 221004, ChinaCancer Institute, Xuzhou Medical University, 209 Tongshan Road, Xuzhou, Jiangsu, 221004, China; Center of Clinical Oncology, The Affiliated Hospital of Xuzhou Medical University, 99 Huaihai Road, Xuzhou, Jiangsu, 221002, China; Jiangsu Center for the Collaboration and Innovation of Cancer Biotherapy, Xuzhou Medical University, 209 Tongshan Road, Xuzhou, Jiangsu, 221004, ChinaCancer Institute, Xuzhou Medical University, 209 Tongshan Road, Xuzhou, Jiangsu, 221004, China; Center of Clinical Oncology, The Affiliated Hospital of Xuzhou Medical University, 99 Huaihai Road, Xuzhou, Jiangsu, 221002, China; Jiangsu Center for the Collaboration and Innovation of Cancer Biotherapy, Xuzhou Medical University, 209 Tongshan Road, Xuzhou, Jiangsu, 221004, ChinaCancer Institute, Xuzhou Medical University, 209 Tongshan Road, Xuzhou, Jiangsu, 221004, China; Center of Clinical Oncology, The Affiliated Hospital of Xuzhou Medical University, 99 Huaihai Road, Xuzhou, Jiangsu, 221002, China; Jiangsu Center for the Collaboration and Innovation of Cancer Biotherapy, Xuzhou Medical University, 209 Tongshan Road, Xuzhou, Jiangsu, 221004, ChinaCancer Institute, Xuzhou Medical University, 209 Tongshan Road, Xuzhou, Jiangsu, 221004, China; Center of Clinical Oncology, The Affiliated Hospital of Xuzhou Medical University, 99 Huaihai Road, Xuzhou, Jiangsu, 221002, China; Jiangsu Center for the Collaboration and Innovation of Cancer Biotherapy, Xuzhou Medical University, 209 Tongshan Road, Xuzhou, Jiangsu, 221004, ChinaCancer Institute, Xuzhou Medical University, 209 Tongshan Road, Xuzhou, Jiangsu, 221004, China; Center of Clinical Oncology, The Affiliated Hospital of Xuzhou Medical University, 99 Huaihai Road, Xuzhou, Jiangsu, 221002, China; Jiangsu Center for the Collaboration and Innovation of Cancer Biotherapy, Xuzhou Medical University, 209 Tongshan Road, Xuzhou, Jiangsu, 221004, ChinaCancer Institute, Xuzhou Medical University, 209 Tongshan Road, Xuzhou, Jiangsu, 221004, China; Center of Clinical Oncology, The Affiliated Hospital of Xuzhou Medical University, 99 Huaihai Road, Xuzhou, Jiangsu, 221002, China; Jiangsu Center for the Collaboration and Innovation of Cancer Biotherapy, Xuzhou Medical University, 209 Tongshan Road, Xuzhou, Jiangsu, 221004, ChinaCancer Institute, Xuzhou Medical University, 209 Tongshan Road, Xuzhou, Jiangsu, 221004, China; Center of Clinical Oncology, The Affiliated Hospital of Xuzhou Medical University, 99 Huaihai Road, Xuzhou, Jiangsu, 221002, China; Jiangsu Center for the Collaboration and Innovation of Cancer Biotherapy, Xuzhou Medical University, 209 Tongshan Road, Xuzhou, Jiangsu, 221004, ChinaCancer Institute, Xuzhou Medical University, 209 Tongshan Road, Xuzhou, Jiangsu, 221004, China; Center of Clinical Oncology, The Affiliated Hospital of Xuzhou Medical University, 99 Huaihai Road, Xuzhou, Jiangsu, 221002, China; Jiangsu Center for the Collaboration and Innovation of Cancer Biotherapy, Xuzhou Medical University, 209 Tongshan Road, Xuzhou, Jiangsu, 221004, China; Corresponding author. Cancer Institute, Xuzhou Medical University, 209 Tongshan Road, Xuzhou, Jiangsu, 221004, China.Cancer Institute, Xuzhou Medical University, 209 Tongshan Road, Xuzhou, Jiangsu, 221004, China; Center of Clinical Oncology, The Affiliated Hospital of Xuzhou Medical University, 99 Huaihai Road, Xuzhou, Jiangsu, 221002, China; Jiangsu Center for the Collaboration and Innovation of Cancer Biotherapy, Xuzhou Medical University, 209 Tongshan Road, Xuzhou, Jiangsu, 221004, China; Corresponding author. Cancer Institute, Xuzhou Medical University, 209 Tongshan Road, Xuzhou, Jiangsu, 221004, China.Triple-negative breast cancer (TNBC), characterized by negative expression of estrogen receptor, progesterone receptor, and oncogene HER-2, always exhibits resistance to targeted drugs. Immunotherapies have demonstrated promising clinical responses and significant potential for TNBC treatment. Enhancing and activating antitumoral immunity can help restrain TNBC progression. In this work, we developed and validated an irradiation-responsive, tumor-targeting, and pyroptosis-enhanced drug delivery system based on neutrophils for effective TNBC treatment. Specifically, TNBC cell membrane-derived liposomes were loaded with photothermal agent IR775 and a pyroptosis-promoting plasmid carrying GSDME coding sequence (GI-LNPs). These GI-LNPs were then anchored onto the surface of neutrophils via biotin-avidin interaction and delivered into the tumor through local injury-driven neutrophil infiltration. Compared to conventional therapeutic strategies, NE-GI-LNPs accumulated and penetrated more deeply into tumor tissues. Furthermore, IR775-triggered the generation of caspase-3 under NIR laser irradiation promoted the cleavage of expressed GSDME, converting apoptosis to pyroptosis in 4T1 cells and enhancing antitumor immunity. Overall, our study demonstrated that multifunctional GI-LNPs delivered by neutrophils could effectively inhibit tumor growth through pyroptosis-enhanced antitumor immunotherapy.http://www.sciencedirect.com/science/article/pii/S2590006425004740Triple-negative breast cancerNeutrophilsCell membrane-derived liposomesPyroptosisImmunotherapy |
| spellingShingle | Ge Gao Xiaodi Xu Xiaoyang Liu Yao-Wen Jiang Meng Wang Tong Su Jiaxuan Chen Mingxia Xue Weixiang Zhong Yuxin Chen Peng Jiang Junnian Zheng Gang Wang Homologous targeted neutrophils-liposome system for pyroptosis-enhanced antitumor immunotherapy of triple-negative breast cancer Materials Today Bio Triple-negative breast cancer Neutrophils Cell membrane-derived liposomes Pyroptosis Immunotherapy |
| title | Homologous targeted neutrophils-liposome system for pyroptosis-enhanced antitumor immunotherapy of triple-negative breast cancer |
| title_full | Homologous targeted neutrophils-liposome system for pyroptosis-enhanced antitumor immunotherapy of triple-negative breast cancer |
| title_fullStr | Homologous targeted neutrophils-liposome system for pyroptosis-enhanced antitumor immunotherapy of triple-negative breast cancer |
| title_full_unstemmed | Homologous targeted neutrophils-liposome system for pyroptosis-enhanced antitumor immunotherapy of triple-negative breast cancer |
| title_short | Homologous targeted neutrophils-liposome system for pyroptosis-enhanced antitumor immunotherapy of triple-negative breast cancer |
| title_sort | homologous targeted neutrophils liposome system for pyroptosis enhanced antitumor immunotherapy of triple negative breast cancer |
| topic | Triple-negative breast cancer Neutrophils Cell membrane-derived liposomes Pyroptosis Immunotherapy |
| url | http://www.sciencedirect.com/science/article/pii/S2590006425004740 |
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