Enhancing tumor immunotherapy with smart nanoparticles for reprogramming macrophages and blocking the CD47/Sirpα pathway
Immunotherapy has significantly advanced cancer treatment, but the tumor immune microenvironment (TIME) often remains immunosuppressive, limiting therapeutic efficacy. Tumor-associated macrophages (TAMs), particularly M2-like macrophages, play a crucial role in promoting tumor growth and immune evas...
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| Language: | English |
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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/S2590006425003862 |
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| author | Zubair Hussain Shanshan Gou Xu Liu Mengyu Li Hanyue Zhang Sumei Ren Ruxia Han Fangfang Liu Xiaowen Zhou Lu Qiu Hongfei Wang Zhenzhen Chen Kangdong Liu |
| author_facet | Zubair Hussain Shanshan Gou Xu Liu Mengyu Li Hanyue Zhang Sumei Ren Ruxia Han Fangfang Liu Xiaowen Zhou Lu Qiu Hongfei Wang Zhenzhen Chen Kangdong Liu |
| author_sort | Zubair Hussain |
| collection | DOAJ |
| description | Immunotherapy has significantly advanced cancer treatment, but the tumor immune microenvironment (TIME) often remains immunosuppressive, limiting therapeutic efficacy. Tumor-associated macrophages (TAMs), particularly M2-like macrophages, play a crucial role in promoting tumor growth and immune evasion. Our study introduces a novel approach using dual-targeted ZrMOF/C@P nanoparticles, smartly engineered with cell membrane coating and enzyme responsiveness, to effectively modulate TAMs. These nanoparticles are synthesized and loaded with 2′, 3′-cGAMP, a STING agonist, and encapsulated in a peptide-expressed macrophage membrane (PMM) featuring Pep20, MMP2, and M2pep. In vitro, they activate the STING pathway in M2-like macrophages and reprogram them into M1-like macrophages. Smart ZrMOF/C@P is found to accumulate at the tumor even 72 h post-injection. In CT26 and 4T1 tumor models show that smart ZrMOF/C@P not only suppresses tumor growth but also stimulates systemic immune responses. This is evidenced by a reduction in M2-like and an increase in M1-like macrophages, enhanced dendritic cell (DC) maturation, and increased tumor infiltration of CD4+ and CD8+ T cells, accompanied by elevated IFN-γ secretion. This innovative use of ZrMOF/C@P offers a promising strategy to transform the immunosuppressive TIME, presenting a versatile and effective treatment option for solid tumors, and novel avenue for non-CDN-STING agonists, facilitating systemic administration. |
| format | Article |
| id | doaj-art-c7c17ceceb2e492bb5eb4ece2d5449a4 |
| institution | OA Journals |
| issn | 2590-0064 |
| language | English |
| publishDate | 2025-06-01 |
| publisher | Elsevier |
| record_format | Article |
| series | Materials Today Bio |
| spelling | doaj-art-c7c17ceceb2e492bb5eb4ece2d5449a42025-08-20T01:51:00ZengElsevierMaterials Today Bio2590-00642025-06-013210182610.1016/j.mtbio.2025.101826Enhancing tumor immunotherapy with smart nanoparticles for reprogramming macrophages and blocking the CD47/Sirpα pathwayZubair Hussain0Shanshan Gou1Xu Liu2Mengyu Li3Hanyue Zhang4Sumei Ren5Ruxia Han6Fangfang Liu7Xiaowen Zhou8Lu Qiu9Hongfei Wang10Zhenzhen Chen11Kangdong Liu12State Key Laboratory of Metabolic Dysregulation & Prevention and Treatment of Esophageal Cancer, The School of Basic Medical Sciences, Zhengzhou University, Zhengzhou, 450000, China; Tianjian Laboratory of Advanced Biomedical Sciences, Academy of Medical Sciences, Zhengzhou University, Zhengzhou, Henan, 450001, China; Cancer Chemoprevention International Collaboration Laboratory, Zhengzhou, Henan, 450000, ChinaTianjian Laboratory of Advanced Biomedical Sciences, Academy of Medical Sciences, Zhengzhou University, Zhengzhou, Henan, 450001, China; Corresponding author. Tianjian Laboratory of Advanced Biomedical Sciences, Academy of Medical Sciences, Zhengzhou University, 100 Kexue Avenue, Zhengzhou, Henan 450001, China.School of Mechanical Engineering, North China University of Water Resources and Electric Power, Zhengzhou, Henan, 450045, ChinaTianjian Laboratory of Advanced Biomedical Sciences, Academy of Medical Sciences, Zhengzhou University, Zhengzhou, Henan, 450001, ChinaTianjian Laboratory of Advanced Biomedical Sciences, Academy of Medical Sciences, Zhengzhou University, Zhengzhou, Henan, 450001, ChinaTianjian Laboratory of Advanced Biomedical Sciences, Academy of Medical Sciences, Zhengzhou University, Zhengzhou, Henan, 450001, ChinaTianjian Laboratory of Advanced Biomedical Sciences, Academy of Medical Sciences, Zhengzhou University, Zhengzhou, Henan, 450001, ChinaState Key Laboratory of Metabolic Dysregulation & Prevention and Treatment of Esophageal Cancer, The School of Basic Medical Sciences, Zhengzhou University, Zhengzhou, 450000, ChinaSchool of Life Sciences, Zhengzhou University, Zhengzhou, Henan, 450001, ChinaDepartment of Pathology, The First Affiliated Hospital of Zhengzhou University, Zhengzhou, Henan, 450000, China; Corresponding author. Department of Pathology, The First Affiliated Hospital of Zhengzhou University, Zhengzhou, Henan, 450000, China.Henan Key Laboratory of Immunology and Targeted Drugs, School of Medical Technology, Xinxiang Medical University, Xinxiang, Henan, 453003, ChinaSchool of Life Sciences, Zhengzhou University, Zhengzhou, Henan, 450001, ChinaState Key Laboratory of Metabolic Dysregulation & Prevention and Treatment of Esophageal Cancer, The School of Basic Medical Sciences, Zhengzhou University, Zhengzhou, 450000, China; Tianjian Laboratory of Advanced Biomedical Sciences, Academy of Medical Sciences, Zhengzhou University, Zhengzhou, Henan, 450001, China; Cancer Chemoprevention International Collaboration Laboratory, Zhengzhou, Henan, 450000, China; China-US (Henan) Hormel Cancer Institute, Zhengzhou, Henan, 450008, China; Corresponding author. Department of Pathophysiology, School of Basic Medical Sciences, Zhengzhou University, 100 Kexue Avenue, Zhengzhou, Henan, 450001, China.Immunotherapy has significantly advanced cancer treatment, but the tumor immune microenvironment (TIME) often remains immunosuppressive, limiting therapeutic efficacy. Tumor-associated macrophages (TAMs), particularly M2-like macrophages, play a crucial role in promoting tumor growth and immune evasion. Our study introduces a novel approach using dual-targeted ZrMOF/C@P nanoparticles, smartly engineered with cell membrane coating and enzyme responsiveness, to effectively modulate TAMs. These nanoparticles are synthesized and loaded with 2′, 3′-cGAMP, a STING agonist, and encapsulated in a peptide-expressed macrophage membrane (PMM) featuring Pep20, MMP2, and M2pep. In vitro, they activate the STING pathway in M2-like macrophages and reprogram them into M1-like macrophages. Smart ZrMOF/C@P is found to accumulate at the tumor even 72 h post-injection. In CT26 and 4T1 tumor models show that smart ZrMOF/C@P not only suppresses tumor growth but also stimulates systemic immune responses. This is evidenced by a reduction in M2-like and an increase in M1-like macrophages, enhanced dendritic cell (DC) maturation, and increased tumor infiltration of CD4+ and CD8+ T cells, accompanied by elevated IFN-γ secretion. This innovative use of ZrMOF/C@P offers a promising strategy to transform the immunosuppressive TIME, presenting a versatile and effective treatment option for solid tumors, and novel avenue for non-CDN-STING agonists, facilitating systemic administration.http://www.sciencedirect.com/science/article/pii/S2590006425003862Tumor immunotherapyTumor-associated macrophageSTING agonistCD47/Sirpα axisSmart PMM-Expressing cell membrane |
| spellingShingle | Zubair Hussain Shanshan Gou Xu Liu Mengyu Li Hanyue Zhang Sumei Ren Ruxia Han Fangfang Liu Xiaowen Zhou Lu Qiu Hongfei Wang Zhenzhen Chen Kangdong Liu Enhancing tumor immunotherapy with smart nanoparticles for reprogramming macrophages and blocking the CD47/Sirpα pathway Materials Today Bio Tumor immunotherapy Tumor-associated macrophage STING agonist CD47/Sirpα axis Smart PMM-Expressing cell membrane |
| title | Enhancing tumor immunotherapy with smart nanoparticles for reprogramming macrophages and blocking the CD47/Sirpα pathway |
| title_full | Enhancing tumor immunotherapy with smart nanoparticles for reprogramming macrophages and blocking the CD47/Sirpα pathway |
| title_fullStr | Enhancing tumor immunotherapy with smart nanoparticles for reprogramming macrophages and blocking the CD47/Sirpα pathway |
| title_full_unstemmed | Enhancing tumor immunotherapy with smart nanoparticles for reprogramming macrophages and blocking the CD47/Sirpα pathway |
| title_short | Enhancing tumor immunotherapy with smart nanoparticles for reprogramming macrophages and blocking the CD47/Sirpα pathway |
| title_sort | enhancing tumor immunotherapy with smart nanoparticles for reprogramming macrophages and blocking the cd47 sirpα pathway |
| topic | Tumor immunotherapy Tumor-associated macrophage STING agonist CD47/Sirpα axis Smart PMM-Expressing cell membrane |
| url | http://www.sciencedirect.com/science/article/pii/S2590006425003862 |
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