Pancreatic cancer-targeting exosomes for enhancing immunotherapy and reprogramming tumor microenvironment
Immunotherapy has gained increasing focus in treating pancreatic ductal adenocarcinoma (PDAC), since conventional therapies like chemotherapy could not provide satisfactory improvement in overall survival outcome of PDAC patients. However, it is still not the game changing solution due to the unique...
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| Published in | Biomaterials Vol. 268; p. 120546 |
|---|---|
| Main Authors | , , , , , , , , , , , , |
| Format | Journal Article |
| Language | English |
| Published |
Netherlands
Elsevier Ltd
01.01.2021
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| Subjects | |
| Online Access | Get full text |
| ISSN | 0142-9612 1878-5905 1878-5905 |
| DOI | 10.1016/j.biomaterials.2020.120546 |
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| Abstract | Immunotherapy has gained increasing focus in treating pancreatic ductal adenocarcinoma (PDAC), since conventional therapies like chemotherapy could not provide satisfactory improvement in overall survival outcome of PDAC patients. However, it is still not the game changing solution due to the unique tumor microenvironment and low cancer immunogenicity of PDAC. Thus, inducing more intratumoral effector immune cells as well as reversing immunosuppression is the core of PDAC treatment. Herein, we demonstrate an exosome-based dual delivery biosystem for enhancing PDAC immunotherapy as well as reversing tumor immunosuppression of M2-like tumor associated macrophages (M2-TAMs) upon disruption of galectin-9/dectin 1 axis. The deliver system is constructed from bone marrow mesenchymal stem cell (BM-MSC) exosomes, electroporation-loaded galectin-9 siRNA, and surficially modified with oxaliplatin (OXA) prodrug as an immunogenic cell death (ICD)-trigger. The use of biomaterials, BM-MSC exosomes, can significantly improve tumor targeting efficacy, thus increasing drug accumulation in the tumor site. The combined therapy (iEXO-OXA) elicits anti-tumor immunity through tumor-suppressive macrophage polarization, cytotoxic T lymphocytes recruitment and Tregs downregulation, and achieves significant therapeutic efficacy in cancer treatment.
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| AbstractList | Immunotherapy has gained increasing focus in treating pancreatic ductal adenocarcinoma (PDAC), since conventional therapies like chemotherapy could not provide satisfactory improvement in overall survival outcome of PDAC patients. However, it is still not the game changing solution due to the unique tumor microenvironment and low cancer immunogenicity of PDAC. Thus, inducing more intratumoral effector immune cells as well as reversing immunosuppression is the core of PDAC treatment. Herein, we demonstrate an exosome-based dual delivery biosystem for enhancing PDAC immunotherapy as well as reversing tumor immunosuppression of M2-like tumor associated macrophages (M2-TAMs) upon disruption of galectin-9/dectin 1 axis. The deliver system is constructed from bone marrow mesenchymal stem cell (BM-MSC) exosomes, electroporation-loaded galectin-9 siRNA, and surficially modified with oxaliplatin (OXA) prodrug as an immunogenic cell death (ICD)-trigger. The use of biomaterials, BM-MSC exosomes, can significantly improve tumor targeting efficacy, thus increasing drug accumulation in the tumor site. The combined therapy (iEXO-OXA) elicits anti-tumor immunity through tumor-suppressive macrophage polarization, cytotoxic T lymphocytes recruitment and Tregs downregulation, and achieves significant therapeutic efficacy in cancer treatment.
[Display omitted] Immunotherapy has gained increasing focus in treating pancreatic ductal adenocarcinoma (PDAC), since conventional therapies like chemotherapy could not provide satisfactory improvement in overall survival outcome of PDAC patients. However, it is still not the game changing solution due to the unique tumor microenvironment and low cancer immunogenicity of PDAC. Thus, inducing more intratumoral effector immune cells as well as reversing immunosuppression is the core of PDAC treatment. Herein, we demonstrate an exosome-based dual delivery biosystem for enhancing PDAC immunotherapy as well as reversing tumor immunosuppression of M2-like tumor associated macrophages (M2-TAMs) upon disruption of galectin-9/dectin 1 axis. The deliver system is constructed from bone marrow mesenchymal stem cell (BM-MSC) exosomes, electroporation-loaded galectin-9 siRNA, and surficially modified with oxaliplatin (OXA) prodrug as an immunogenic cell death (ICD)-trigger. The use of biomaterials, BM-MSC exosomes, can significantly improve tumor targeting efficacy, thus increasing drug accumulation in the tumor site. The combined therapy (iEXO-OXA) elicits anti-tumor immunity through tumor-suppressive macrophage polarization, cytotoxic T lymphocytes recruitment and Tregs downregulation, and achieves significant therapeutic efficacy in cancer treatment. Immunotherapy has gained increasing focus in treating pancreatic ductal adenocarcinoma (PDAC), since conventional therapies like chemotherapy could not provide satisfactory improvement in overall survival outcome of PDAC patients. However, it is still not the game changing solution due to the unique tumor microenvironment and low cancer immunogenicity of PDAC. Thus, inducing more intratumoral effector immune cells as well as reversing immunosuppression is the core of PDAC treatment. Herein, we demonstrate an exosome-based dual delivery biosystem for enhancing PDAC immunotherapy as well as reversing tumor immunosuppression of M2-like tumor associated macrophages (M2-TAMs) upon disruption of galectin-9/dectin 1 axis. The deliver system is constructed from bone marrow mesenchymal stem cell (BM-MSC) exosomes, electroporation-loaded galectin-9 siRNA, and surficially modified with oxaliplatin (OXA) prodrug as an immunogenic cell death (ICD)-trigger. The use of biomaterials, BM-MSC exosomes, can significantly improve tumor targeting efficacy, thus increasing drug accumulation in the tumor site. The combined therapy (iEXO-OXA) elicits anti-tumor immunity through tumor-suppressive macrophage polarization, cytotoxic T lymphocytes recruitment and Tregs downregulation, and achieves significant therapeutic efficacy in cancer treatment.Immunotherapy has gained increasing focus in treating pancreatic ductal adenocarcinoma (PDAC), since conventional therapies like chemotherapy could not provide satisfactory improvement in overall survival outcome of PDAC patients. However, it is still not the game changing solution due to the unique tumor microenvironment and low cancer immunogenicity of PDAC. Thus, inducing more intratumoral effector immune cells as well as reversing immunosuppression is the core of PDAC treatment. Herein, we demonstrate an exosome-based dual delivery biosystem for enhancing PDAC immunotherapy as well as reversing tumor immunosuppression of M2-like tumor associated macrophages (M2-TAMs) upon disruption of galectin-9/dectin 1 axis. The deliver system is constructed from bone marrow mesenchymal stem cell (BM-MSC) exosomes, electroporation-loaded galectin-9 siRNA, and surficially modified with oxaliplatin (OXA) prodrug as an immunogenic cell death (ICD)-trigger. The use of biomaterials, BM-MSC exosomes, can significantly improve tumor targeting efficacy, thus increasing drug accumulation in the tumor site. The combined therapy (iEXO-OXA) elicits anti-tumor immunity through tumor-suppressive macrophage polarization, cytotoxic T lymphocytes recruitment and Tregs downregulation, and achieves significant therapeutic efficacy in cancer treatment. |
| ArticleNumber | 120546 |
| Author | Chen, Hongyi Zhou, Yu Zhang, Yiwen Sun, Tao Zhou, Wenxi Chen, Xinli Zhang, Yujie Chu, Yongchao Guo, Qin Jiang, Chen Ning, Tingting Li, Chao Liu, Peixin |
| Author_xml | – sequence: 1 givenname: Wenxi surname: Zhou fullname: Zhou, Wenxi organization: Key Laboratory of Smart Drug Delivery, Ministry of Education, State Key Laboratory of Medical Neurobiology and MOE Frontiers Center for Brain Science, Department of Pharmaceutics, School of Pharmacy, Fudan University, Shanghai, 201203, China – sequence: 2 givenname: Yu surname: Zhou fullname: Zhou, Yu organization: Department of Interventional Radiology, Ruijin Hospital, Shanghai Jiao Tong University, School of Medicine, Shanghai, 200025, China – sequence: 3 givenname: Xinli surname: Chen fullname: Chen, Xinli organization: Key Laboratory of Smart Drug Delivery, Ministry of Education, State Key Laboratory of Medical Neurobiology and MOE Frontiers Center for Brain Science, Department of Pharmaceutics, School of Pharmacy, Fudan University, Shanghai, 201203, China – sequence: 4 givenname: Tingting surname: Ning fullname: Ning, Tingting organization: Key Laboratory of Smart Drug Delivery, Ministry of Education, State Key Laboratory of Medical Neurobiology and MOE Frontiers Center for Brain Science, Department of Pharmaceutics, School of Pharmacy, Fudan University, Shanghai, 201203, China – sequence: 5 givenname: Hongyi surname: Chen fullname: Chen, Hongyi organization: Key Laboratory of Smart Drug Delivery, Ministry of Education, State Key Laboratory of Medical Neurobiology and MOE Frontiers Center for Brain Science, Department of Pharmaceutics, School of Pharmacy, Fudan University, Shanghai, 201203, China – sequence: 6 givenname: Qin surname: Guo fullname: Guo, Qin organization: Key Laboratory of Smart Drug Delivery, Ministry of Education, State Key Laboratory of Medical Neurobiology and MOE Frontiers Center for Brain Science, Department of Pharmaceutics, School of Pharmacy, Fudan University, Shanghai, 201203, China – sequence: 7 givenname: Yiwen surname: Zhang fullname: Zhang, Yiwen organization: Key Laboratory of Smart Drug Delivery, Ministry of Education, State Key Laboratory of Medical Neurobiology and MOE Frontiers Center for Brain Science, Department of Pharmaceutics, School of Pharmacy, Fudan University, Shanghai, 201203, China – sequence: 8 givenname: Peixin surname: Liu fullname: Liu, Peixin organization: Key Laboratory of Smart Drug Delivery, Ministry of Education, State Key Laboratory of Medical Neurobiology and MOE Frontiers Center for Brain Science, Department of Pharmaceutics, School of Pharmacy, Fudan University, Shanghai, 201203, China – sequence: 9 givenname: Yujie surname: Zhang fullname: Zhang, Yujie organization: Key Laboratory of Smart Drug Delivery, Ministry of Education, State Key Laboratory of Medical Neurobiology and MOE Frontiers Center for Brain Science, Department of Pharmaceutics, School of Pharmacy, Fudan University, Shanghai, 201203, China – sequence: 10 givenname: Chao surname: Li fullname: Li, Chao organization: Key Laboratory of Smart Drug Delivery, Ministry of Education, State Key Laboratory of Medical Neurobiology and MOE Frontiers Center for Brain Science, Department of Pharmaceutics, School of Pharmacy, Fudan University, Shanghai, 201203, China – sequence: 11 givenname: Yongchao surname: Chu fullname: Chu, Yongchao organization: Key Laboratory of Smart Drug Delivery, Ministry of Education, State Key Laboratory of Medical Neurobiology and MOE Frontiers Center for Brain Science, Department of Pharmaceutics, School of Pharmacy, Fudan University, Shanghai, 201203, China – sequence: 12 givenname: Tao surname: Sun fullname: Sun, Tao organization: Key Laboratory of Smart Drug Delivery, Ministry of Education, State Key Laboratory of Medical Neurobiology and MOE Frontiers Center for Brain Science, Department of Pharmaceutics, School of Pharmacy, Fudan University, Shanghai, 201203, China – sequence: 13 givenname: Chen surname: Jiang fullname: Jiang, Chen email: jiangchen@shmu.edu.cn organization: Key Laboratory of Smart Drug Delivery, Ministry of Education, State Key Laboratory of Medical Neurobiology and MOE Frontiers Center for Brain Science, Department of Pharmaceutics, School of Pharmacy, Fudan University, Shanghai, 201203, China |
| BackLink | https://www.ncbi.nlm.nih.gov/pubmed/33253966$$D View this record in MEDLINE/PubMed |
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| Title | Pancreatic cancer-targeting exosomes for enhancing immunotherapy and reprogramming tumor microenvironment |
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