Development of a bacteria-nanosapper for the active delivery of ZIF-8 particles containing therapeutic genes for cancer immune therapy
Specific tumor-targeted gene delivery remains an unsolved therapeutic issue due to aberrant vascularization in tumor microenvironment (TME). Some bacteria exhibit spontaneous chemotaxis toward the anaerobic and immune-suppressive TME, which makes them ideal natural vehicles for cancer gene therapy....
Saved in:
| Main Authors: | , , , , , , , , , , , |
|---|---|
| Format: | Article |
| Language: | English |
| Published: |
Elsevier
2024-12-01
|
| Series: | Acta Pharmaceutica Sinica B |
| Subjects: | |
| Online Access: | http://www.sciencedirect.com/science/article/pii/S2211383524003101 |
| Tags: |
Add Tag
No Tags, Be the first to tag this record!
|
| _version_ | 1846117927946813440 |
|---|---|
| author | Yiting Qiao Miao Luo Yufei Wang Haoxiang Qi Menglan Wang Yunxin Pei Mengqing Sun Zhengguo Zhang Jiacheng Huang Pengyu Gong Shusen Zheng Jianxiang Chen |
| author_facet | Yiting Qiao Miao Luo Yufei Wang Haoxiang Qi Menglan Wang Yunxin Pei Mengqing Sun Zhengguo Zhang Jiacheng Huang Pengyu Gong Shusen Zheng Jianxiang Chen |
| author_sort | Yiting Qiao |
| collection | DOAJ |
| description | Specific tumor-targeted gene delivery remains an unsolved therapeutic issue due to aberrant vascularization in tumor microenvironment (TME). Some bacteria exhibit spontaneous chemotaxis toward the anaerobic and immune-suppressive TME, which makes them ideal natural vehicles for cancer gene therapy. Here, we conjugated ZIF-8 metal-organic frameworks encapsulating eukaryotic murine interleukin 2 (Il2) expression plasmid onto the surface of VNP20009, an attenuated Salmonella typhimurium strain with well-documented anti-cancer activity, and constructed a TME-targeted Il2 delivery system named Il2/ZIF-8@Salmonella. Both in vitro and in vivo experiments demonstrated that Il2/ZIF-8@Salmonella maintained the tumor-targeting feature of bacteria, and could be effectively phagocytosed by intratumoral macrophages, thus leading to the expression and secretion of IL2 in TME. The detailed analysis of tumor immune microenvironment (TIME) showed that one dose of combinatorial Il2/ZIF-8@Salmonella achieved synergistic actions on a potent remodeling of TIME, marked by the activation of cytotoxic T cells and M1-polarization of macrophages in TME, thus leading to significant anti-tumor effects in melanoma, orthotopic hepatocellular carcinoma, and pulmonary metastasis models. More importantly, Il2/ZIF-8@Salmonella exhibited high safety to major organs and hematopoietic systems. Taken together, we report a novel plasmid/ZIF-8@Salmonella system that simultaneously achieves effective TME-targeted delivery of therapeutic gene, as well as synergistic re-activation of TIME. |
| format | Article |
| id | doaj-art-bb67f3192552430db9bcd7f982a7f7d7 |
| institution | Kabale University |
| issn | 2211-3835 |
| language | English |
| publishDate | 2024-12-01 |
| publisher | Elsevier |
| record_format | Article |
| series | Acta Pharmaceutica Sinica B |
| spelling | doaj-art-bb67f3192552430db9bcd7f982a7f7d72024-12-18T08:48:42ZengElsevierActa Pharmaceutica Sinica B2211-38352024-12-01141254185434Development of a bacteria-nanosapper for the active delivery of ZIF-8 particles containing therapeutic genes for cancer immune therapyYiting Qiao0Miao Luo1Yufei Wang2Haoxiang Qi3Menglan Wang4Yunxin Pei5Mengqing Sun6Zhengguo Zhang7Jiacheng Huang8Pengyu Gong9Shusen Zheng10Jianxiang Chen11Division of Hepatobiliary and Pancreatic Surgery, Department of Surgery, The First Affiliated Hospital, Zhejiang University School of Medicine, Hangzhou 310003, China; School of Pharmacy, Institute of Hepatology and Metabolic Diseases, Department of Hepatology, the Affiliated Hospital of Hangzhou Normal University, Hangzhou Normal University, Hangzhou 311121, China; Jinan Microecological Biomedicine Shandong Laboratory, Jinan 250000, China; NHC Key Laboratory of Combined Multi-organ Transplantation, Key Laboratory of Organ Transplantation, Hangzhou 310003, China; Key Laboratory of the Diagnosis and Treatment of Organ Transplantation, Research Unit of Collaborative Diagnosis and Treatment For Hepatobiliary and Pancreatic Cancer, Chinese Academy of Medical Science (2019RU019), Hangzhou 310003, China; Corresponding authors.School of Pharmacy, Institute of Hepatology and Metabolic Diseases, Department of Hepatology, the Affiliated Hospital of Hangzhou Normal University, Hangzhou Normal University, Hangzhou 311121, China; Key Laboratory of Digital Technology in Medical Diagnostics of Zhejiang Province, Dian Diagnostics Group Co., Ltd., Hangzhou 310000, ChinaSchool of Pharmacy, Institute of Hepatology and Metabolic Diseases, Department of Hepatology, the Affiliated Hospital of Hangzhou Normal University, Hangzhou Normal University, Hangzhou 311121, ChinaSchool of Pharmacy, Institute of Hepatology and Metabolic Diseases, Department of Hepatology, the Affiliated Hospital of Hangzhou Normal University, Hangzhou Normal University, Hangzhou 311121, ChinaSchool of Pharmacy, Institute of Hepatology and Metabolic Diseases, Department of Hepatology, the Affiliated Hospital of Hangzhou Normal University, Hangzhou Normal University, Hangzhou 311121, ChinaSchool of Pharmacy, Institute of Hepatology and Metabolic Diseases, Department of Hepatology, the Affiliated Hospital of Hangzhou Normal University, Hangzhou Normal University, Hangzhou 311121, ChinaSchool of Pharmacy, Institute of Hepatology and Metabolic Diseases, Department of Hepatology, the Affiliated Hospital of Hangzhou Normal University, Hangzhou Normal University, Hangzhou 311121, ChinaSchool of Pharmacy, Institute of Hepatology and Metabolic Diseases, Department of Hepatology, the Affiliated Hospital of Hangzhou Normal University, Hangzhou Normal University, Hangzhou 311121, ChinaDivision of Hepatobiliary and Pancreatic Surgery, Department of Surgery, The First Affiliated Hospital, Zhejiang University School of Medicine, Hangzhou 310003, ChinaSchool of Pharmacy, Institute of Hepatology and Metabolic Diseases, Department of Hepatology, the Affiliated Hospital of Hangzhou Normal University, Hangzhou Normal University, Hangzhou 311121, ChinaDivision of Hepatobiliary and Pancreatic Surgery, Department of Surgery, The First Affiliated Hospital, Zhejiang University School of Medicine, Hangzhou 310003, China; NHC Key Laboratory of Combined Multi-organ Transplantation, Key Laboratory of Organ Transplantation, Hangzhou 310003, China; Key Laboratory of the Diagnosis and Treatment of Organ Transplantation, Research Unit of Collaborative Diagnosis and Treatment For Hepatobiliary and Pancreatic Cancer, Chinese Academy of Medical Science (2019RU019), Hangzhou 310003, ChinaSchool of Pharmacy, Institute of Hepatology and Metabolic Diseases, Department of Hepatology, the Affiliated Hospital of Hangzhou Normal University, Hangzhou Normal University, Hangzhou 311121, China; Corresponding authors.Specific tumor-targeted gene delivery remains an unsolved therapeutic issue due to aberrant vascularization in tumor microenvironment (TME). Some bacteria exhibit spontaneous chemotaxis toward the anaerobic and immune-suppressive TME, which makes them ideal natural vehicles for cancer gene therapy. Here, we conjugated ZIF-8 metal-organic frameworks encapsulating eukaryotic murine interleukin 2 (Il2) expression plasmid onto the surface of VNP20009, an attenuated Salmonella typhimurium strain with well-documented anti-cancer activity, and constructed a TME-targeted Il2 delivery system named Il2/ZIF-8@Salmonella. Both in vitro and in vivo experiments demonstrated that Il2/ZIF-8@Salmonella maintained the tumor-targeting feature of bacteria, and could be effectively phagocytosed by intratumoral macrophages, thus leading to the expression and secretion of IL2 in TME. The detailed analysis of tumor immune microenvironment (TIME) showed that one dose of combinatorial Il2/ZIF-8@Salmonella achieved synergistic actions on a potent remodeling of TIME, marked by the activation of cytotoxic T cells and M1-polarization of macrophages in TME, thus leading to significant anti-tumor effects in melanoma, orthotopic hepatocellular carcinoma, and pulmonary metastasis models. More importantly, Il2/ZIF-8@Salmonella exhibited high safety to major organs and hematopoietic systems. Taken together, we report a novel plasmid/ZIF-8@Salmonella system that simultaneously achieves effective TME-targeted delivery of therapeutic gene, as well as synergistic re-activation of TIME.http://www.sciencedirect.com/science/article/pii/S2211383524003101Bacteria-mediated cancer therapyVNP20009ZIF-8Gene deliveryTumor microenvironmentTumor immune microenvironment |
| spellingShingle | Yiting Qiao Miao Luo Yufei Wang Haoxiang Qi Menglan Wang Yunxin Pei Mengqing Sun Zhengguo Zhang Jiacheng Huang Pengyu Gong Shusen Zheng Jianxiang Chen Development of a bacteria-nanosapper for the active delivery of ZIF-8 particles containing therapeutic genes for cancer immune therapy Acta Pharmaceutica Sinica B Bacteria-mediated cancer therapy VNP20009 ZIF-8 Gene delivery Tumor microenvironment Tumor immune microenvironment |
| title | Development of a bacteria-nanosapper for the active delivery of ZIF-8 particles containing therapeutic genes for cancer immune therapy |
| title_full | Development of a bacteria-nanosapper for the active delivery of ZIF-8 particles containing therapeutic genes for cancer immune therapy |
| title_fullStr | Development of a bacteria-nanosapper for the active delivery of ZIF-8 particles containing therapeutic genes for cancer immune therapy |
| title_full_unstemmed | Development of a bacteria-nanosapper for the active delivery of ZIF-8 particles containing therapeutic genes for cancer immune therapy |
| title_short | Development of a bacteria-nanosapper for the active delivery of ZIF-8 particles containing therapeutic genes for cancer immune therapy |
| title_sort | development of a bacteria nanosapper for the active delivery of zif 8 particles containing therapeutic genes for cancer immune therapy |
| topic | Bacteria-mediated cancer therapy VNP20009 ZIF-8 Gene delivery Tumor microenvironment Tumor immune microenvironment |
| url | http://www.sciencedirect.com/science/article/pii/S2211383524003101 |
| work_keys_str_mv | AT yitingqiao developmentofabacteriananosapperfortheactivedeliveryofzif8particlescontainingtherapeuticgenesforcancerimmunetherapy AT miaoluo developmentofabacteriananosapperfortheactivedeliveryofzif8particlescontainingtherapeuticgenesforcancerimmunetherapy AT yufeiwang developmentofabacteriananosapperfortheactivedeliveryofzif8particlescontainingtherapeuticgenesforcancerimmunetherapy AT haoxiangqi developmentofabacteriananosapperfortheactivedeliveryofzif8particlescontainingtherapeuticgenesforcancerimmunetherapy AT menglanwang developmentofabacteriananosapperfortheactivedeliveryofzif8particlescontainingtherapeuticgenesforcancerimmunetherapy AT yunxinpei developmentofabacteriananosapperfortheactivedeliveryofzif8particlescontainingtherapeuticgenesforcancerimmunetherapy AT mengqingsun developmentofabacteriananosapperfortheactivedeliveryofzif8particlescontainingtherapeuticgenesforcancerimmunetherapy AT zhengguozhang developmentofabacteriananosapperfortheactivedeliveryofzif8particlescontainingtherapeuticgenesforcancerimmunetherapy AT jiachenghuang developmentofabacteriananosapperfortheactivedeliveryofzif8particlescontainingtherapeuticgenesforcancerimmunetherapy AT pengyugong developmentofabacteriananosapperfortheactivedeliveryofzif8particlescontainingtherapeuticgenesforcancerimmunetherapy AT shusenzheng developmentofabacteriananosapperfortheactivedeliveryofzif8particlescontainingtherapeuticgenesforcancerimmunetherapy AT jianxiangchen developmentofabacteriananosapperfortheactivedeliveryofzif8particlescontainingtherapeuticgenesforcancerimmunetherapy |