Injectable versatile liquid-solid transformation implants alliance checkpoint blockade for magnetothermal dynamic-immunotherapy
The ongoing circulating energy loss, low reactive oxygen species (ROS) accumulation and poor immunogenicity of tumors make it difficult to induce sufficient immunogenic cell death (ICD) in the tumor immunosuppressive microenvironment (TIME), resulting in unsatisfactory immunotherapy efficacy. Furthe...
| Main Authors: | , , , , , , , |
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| Format: | Article |
| Language: | English |
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Elsevier
2022-12-01
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| Series: | Materials Today Bio |
| Subjects: | |
| Online Access: | http://www.sciencedirect.com/science/article/pii/S259000642200240X |
| _version_ | 1798030777042075648 |
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| author | Mengna Wang Siyu Deng Yijia Cao Hang Zhou Wei Wei Kexiao Yu Youde Cao Bing Liang |
| author_facet | Mengna Wang Siyu Deng Yijia Cao Hang Zhou Wei Wei Kexiao Yu Youde Cao Bing Liang |
| author_sort | Mengna Wang |
| collection | DOAJ |
| description | The ongoing circulating energy loss, low reactive oxygen species (ROS) accumulation and poor immunogenicity of tumors make it difficult to induce sufficient immunogenic cell death (ICD) in the tumor immunosuppressive microenvironment (TIME), resulting in unsatisfactory immunotherapy efficacy. Furthermore, for highly malignant tumors, simply enhancing ICD is insufficient for exhaustively eliminating the tumor and inhibiting metastasis. Herein, we propose a unique magnetothermal-dynamic immunotherapy strategy based on liquid-solid transformation porous versatile implants (Fe3O4/AIPH@PLGA) that takes advantage of less energy loss and avoids ongoing circulating losses by minimally invasive injection into tumors. In addition, the magnetothermal effect regresses and eliminates tumors that are not limited by penetration to simultaneously trigger 2,2′-azobis[2-(2-imidazolin-2-yl) propane] dihydrochloride (AIPH) decomposition and generate a large amount of oxygen-irrelevant free radicals and heat shock protein (HSP) accumulation by heating, evoking both intracellular oxidative stress and endoplasmic reticulum (ER) stress to induce large-scale ICD and enhance tumor immunogenicity. More importantly, in orthotopic bilateral breast tumor models, a significant therapeutic effect was obtained after combining amplified ICD with CTLA4 checkpoint blockade. The 21-day primary and distant tumor inhibition rates reached 90%, and the underlying mechanism of the effective synergetic strategy of inducing the T-cell-related response, the immune memory effect and TIME reprogramming in vivo was verified by immune cell analyses. This remarkable therapeutic effect provides a new direction for antitumor immunotherapy based on magnetothermally controlled oxygen-independent free radical release. |
| first_indexed | 2024-04-11T19:46:45Z |
| format | Article |
| id | doaj.art-2769c133f2ca4dc68ea9ff7f3bdb0d2a |
| institution | Directory Open Access Journal |
| issn | 2590-0064 |
| language | English |
| last_indexed | 2024-04-11T19:46:45Z |
| publishDate | 2022-12-01 |
| publisher | Elsevier |
| record_format | Article |
| series | Materials Today Bio |
| spelling | doaj.art-2769c133f2ca4dc68ea9ff7f3bdb0d2a2022-12-22T04:06:27ZengElsevierMaterials Today Bio2590-00642022-12-0116100442Injectable versatile liquid-solid transformation implants alliance checkpoint blockade for magnetothermal dynamic-immunotherapyMengna Wang0Siyu Deng1Yijia Cao2Hang Zhou3Wei Wei4Kexiao Yu5Youde Cao6Bing Liang7Department of Pathology, College of Basic Medicine, Chongqing Medical University, Chongqing, 400016, PR China; Institute of Ultrasound Imaging of Chongqing Medical University; The Second Affiliated Hospital of Chongqing Medical University, 76 Linjiang Road, Yuzhong District, Chongqing, 400010, PR ChinaDepartment of Pathology, College of Basic Medicine, Chongqing Medical University, Chongqing, 400016, PR ChinaDepartment of Digestion, University-Town Hospital of Chongqing Medical University, Chongqing, 401331, PR ChinaInstitute of Ultrasound Imaging of Chongqing Medical University; The Second Affiliated Hospital of Chongqing Medical University, 76 Linjiang Road, Yuzhong District, Chongqing, 400010, PR ChinaDepartment of Pathology, College of Basic Medicine, Chongqing Medical University, Chongqing, 400016, PR ChinaDepartment of Orthopedics, Chongqing Traditional Chinese Medicine Hospital, No. 6 Panxi Seventh Branch Road, Jiangbei District, Chongqing, 400021, PR China; Corresponding author. Department of Orthopedics, Chongqing Traditional Chinese Medicine Hospital, No. 6 Panxi Seventh Branch Road, Jiangbei District, Chongqing, 400021, PR China.Department of Pathology, College of Basic Medicine, Chongqing Medical University, Chongqing, 400016, PR China; Molecular Medicine Diagnostic and Testing Center, Chongqing Medical University, 1 Yixueyuan Road, Yuzhong District, Chongqing, 400016, PR China; Department of Pathology, the First Affiliated Hospital of Chongqing Medical University, 1 Youyi Road, Yuzhong District, Chongqing, 400042, PR China; Corresponding author. Department of Pathology, College of Basic Medicine, Chongqing Medical University, 1 Yixueyuan Road, Yuzhong Distinct, Chongqing, 400016, PR China.Department of Pathology, College of Basic Medicine, Chongqing Medical University, Chongqing, 400016, PR China; Molecular Medicine Diagnostic and Testing Center, Chongqing Medical University, 1 Yixueyuan Road, Yuzhong District, Chongqing, 400016, PR China; Department of Pathology, the First Affiliated Hospital of Chongqing Medical University, 1 Youyi Road, Yuzhong District, Chongqing, 400042, PR China; Corresponding author. Department of Pathology, College of Basic Medicine, Chongqing Medical University, 1 Yixueyuan Road, Yuzhong Distinct, Chongqing, 400016, PR China.The ongoing circulating energy loss, low reactive oxygen species (ROS) accumulation and poor immunogenicity of tumors make it difficult to induce sufficient immunogenic cell death (ICD) in the tumor immunosuppressive microenvironment (TIME), resulting in unsatisfactory immunotherapy efficacy. Furthermore, for highly malignant tumors, simply enhancing ICD is insufficient for exhaustively eliminating the tumor and inhibiting metastasis. Herein, we propose a unique magnetothermal-dynamic immunotherapy strategy based on liquid-solid transformation porous versatile implants (Fe3O4/AIPH@PLGA) that takes advantage of less energy loss and avoids ongoing circulating losses by minimally invasive injection into tumors. In addition, the magnetothermal effect regresses and eliminates tumors that are not limited by penetration to simultaneously trigger 2,2′-azobis[2-(2-imidazolin-2-yl) propane] dihydrochloride (AIPH) decomposition and generate a large amount of oxygen-irrelevant free radicals and heat shock protein (HSP) accumulation by heating, evoking both intracellular oxidative stress and endoplasmic reticulum (ER) stress to induce large-scale ICD and enhance tumor immunogenicity. More importantly, in orthotopic bilateral breast tumor models, a significant therapeutic effect was obtained after combining amplified ICD with CTLA4 checkpoint blockade. The 21-day primary and distant tumor inhibition rates reached 90%, and the underlying mechanism of the effective synergetic strategy of inducing the T-cell-related response, the immune memory effect and TIME reprogramming in vivo was verified by immune cell analyses. This remarkable therapeutic effect provides a new direction for antitumor immunotherapy based on magnetothermally controlled oxygen-independent free radical release.http://www.sciencedirect.com/science/article/pii/S259000642200240XMagnetothermalLiquid-solid transformationImmunogenic cell deathFree radicalsCTLA4 checkpoint blockade |
| spellingShingle | Mengna Wang Siyu Deng Yijia Cao Hang Zhou Wei Wei Kexiao Yu Youde Cao Bing Liang Injectable versatile liquid-solid transformation implants alliance checkpoint blockade for magnetothermal dynamic-immunotherapy Materials Today Bio Magnetothermal Liquid-solid transformation Immunogenic cell death Free radicals CTLA4 checkpoint blockade |
| title | Injectable versatile liquid-solid transformation implants alliance checkpoint blockade for magnetothermal dynamic-immunotherapy |
| title_full | Injectable versatile liquid-solid transformation implants alliance checkpoint blockade for magnetothermal dynamic-immunotherapy |
| title_fullStr | Injectable versatile liquid-solid transformation implants alliance checkpoint blockade for magnetothermal dynamic-immunotherapy |
| title_full_unstemmed | Injectable versatile liquid-solid transformation implants alliance checkpoint blockade for magnetothermal dynamic-immunotherapy |
| title_short | Injectable versatile liquid-solid transformation implants alliance checkpoint blockade for magnetothermal dynamic-immunotherapy |
| title_sort | injectable versatile liquid solid transformation implants alliance checkpoint blockade for magnetothermal dynamic immunotherapy |
| topic | Magnetothermal Liquid-solid transformation Immunogenic cell death Free radicals CTLA4 checkpoint blockade |
| url | http://www.sciencedirect.com/science/article/pii/S259000642200240X |
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