Cancer Immunotherapy Based on the Bidirectional Reprogramming of the Tumor Microenvironment by a “Brakes Off/ Step on the Accelerator” Core‐Shell Manganese Phosphate/siPD‐L1 Modulator
ABSTRACT The insufficient infiltration and functional inhibition of CD8+ T cells due to tumor microenvironment (TME) are considered enormous obstacles to anti‐tumor immunotherapy. Herein, a pH‐responsive core‐shell manganese phosphate nanomodulator co‐loading siPD‐L1 and Mn2+ into nanoparticles coat...
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| Format: | Article |
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Wiley
2025-06-01
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| Series: | Exploration |
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| Online Access: | https://doi.org/10.1002/EXP.70009 |
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| author | Fei Xia Yuqian Lu Zipeng Gong Qingchao Tu Shuntao Liang Chen Wang HaiLu Yao LinYing Zhong Yuanfeng Fu Pengbo Guo Yichong Hou Xinyu Zhou Li Zou Licheng Gan Weiqi Chen Jiawei Yan Junzhe Zhang Huanhuan Pang Yuqing Meng Qiaoli Shi Chen Pan Xiaomei Tao Jigang Wang Qingfeng Du Chong Qiu |
| author_facet | Fei Xia Yuqian Lu Zipeng Gong Qingchao Tu Shuntao Liang Chen Wang HaiLu Yao LinYing Zhong Yuanfeng Fu Pengbo Guo Yichong Hou Xinyu Zhou Li Zou Licheng Gan Weiqi Chen Jiawei Yan Junzhe Zhang Huanhuan Pang Yuqing Meng Qiaoli Shi Chen Pan Xiaomei Tao Jigang Wang Qingfeng Du Chong Qiu |
| author_sort | Fei Xia |
| collection | DOAJ |
| description | ABSTRACT The insufficient infiltration and functional inhibition of CD8+ T cells due to tumor microenvironment (TME) are considered enormous obstacles to anti‐tumor immunotherapy. Herein, a pH‐responsive core‐shell manganese phosphate nanomodulator co‐loading siPD‐L1 and Mn2+ into nanoparticles coated with hyaluronic acid was prepared, which was aimed at the bidirectional reprogramming the tumor microenvironment: (1) “Brakes off,” restoring CD8+ T cells function by siPD‐L1 knockdowning PD‐L1 expression of tumor cells; (2) “Step on the accelerator,” promoting CD8+ T cells infiltration in tumors tissue based on the multidimensional immune effects of Mn2+ (immunogenic cell death induced the enhancing cGAS‐STING pathway, the proliferation and maturation of relative immune cells). Additionally, this strategy could induce macrophage polarization and inhibit the regulatory T cells in tumor site. This work provided a manganese phosphate nanomodulator to reprogram the immune TME for an enhanced comprehensive anti‐tumor effect of triple negative breast cancer, which offers a robust method for tumor immunotherapy in future clinical applications. |
| format | Article |
| id | doaj-art-8dd5ea377b4c47fe9bfee9e32c737de5 |
| institution | OA Journals |
| issn | 2766-8509 2766-2098 |
| language | English |
| publishDate | 2025-06-01 |
| publisher | Wiley |
| record_format | Article |
| series | Exploration |
| spelling | doaj-art-8dd5ea377b4c47fe9bfee9e32c737de52025-08-20T02:36:23ZengWileyExploration2766-85092766-20982025-06-0153n/an/a10.1002/EXP.70009Cancer Immunotherapy Based on the Bidirectional Reprogramming of the Tumor Microenvironment by a “Brakes Off/ Step on the Accelerator” Core‐Shell Manganese Phosphate/siPD‐L1 ModulatorFei Xia0Yuqian Lu1Zipeng Gong2Qingchao Tu3Shuntao Liang4Chen Wang5HaiLu Yao6LinYing Zhong7Yuanfeng Fu8Pengbo Guo9Yichong Hou10Xinyu Zhou11Li Zou12Licheng Gan13Weiqi Chen14Jiawei Yan15Junzhe Zhang16Huanhuan Pang17Yuqing Meng18Qiaoli Shi19Chen Pan20Xiaomei Tao21Jigang Wang22Qingfeng Du23Chong Qiu24State Key Laboratory for Quality Ensurance and Sustainable Use of Dao‐di Herbs, Artemisinin Research Center, and Institute of Chinese Materia Medica China Academy of Chinese Medical Sciences Beijing ChinaState Key Laboratory for Quality Ensurance and Sustainable Use of Dao‐di Herbs, Artemisinin Research Center, and Institute of Chinese Materia Medica China Academy of Chinese Medical Sciences Beijing ChinaState Key Laboratory of Discovery and Utilization of Functional Components in Traditional Chinese Medicine, Guizhou Provincial Engineering Research Center for the Development and Application of Ethnic Medicine and Traditional Chinese Medicine Guizhou Medical University Guiyang ChinaState Key Laboratory for Quality Ensurance and Sustainable Use of Dao‐di Herbs, Artemisinin Research Center, and Institute of Chinese Materia Medica China Academy of Chinese Medical Sciences Beijing ChinaBeiJing Shijitan Hospitals Capital Medical University Beijing ChinaState Key Laboratory for Quality Ensurance and Sustainable Use of Dao‐di Herbs, Artemisinin Research Center, and Institute of Chinese Materia Medica China Academy of Chinese Medical Sciences Beijing ChinaState Key Laboratory for Quality Ensurance and Sustainable Use of Dao‐di Herbs, Artemisinin Research Center, and Institute of Chinese Materia Medica China Academy of Chinese Medical Sciences Beijing ChinaState Key Laboratory for Quality Ensurance and Sustainable Use of Dao‐di Herbs, Artemisinin Research Center, and Institute of Chinese Materia Medica China Academy of Chinese Medical Sciences Beijing ChinaState Key Laboratory for Quality Ensurance and Sustainable Use of Dao‐di Herbs, Artemisinin Research Center, and Institute of Chinese Materia Medica China Academy of Chinese Medical Sciences Beijing ChinaState Key Laboratory for Quality Ensurance and Sustainable Use of Dao‐di Herbs, Artemisinin Research Center, and Institute of Chinese Materia Medica China Academy of Chinese Medical Sciences Beijing ChinaState Key Laboratory for Quality Ensurance and Sustainable Use of Dao‐di Herbs, Artemisinin Research Center, and Institute of Chinese Materia Medica China Academy of Chinese Medical Sciences Beijing ChinaState Key Laboratory for Quality Ensurance and Sustainable Use of Dao‐di Herbs, Artemisinin Research Center, and Institute of Chinese Materia Medica China Academy of Chinese Medical Sciences Beijing ChinaState Key Laboratory for Quality Ensurance and Sustainable Use of Dao‐di Herbs, Artemisinin Research Center, and Institute of Chinese Materia Medica China Academy of Chinese Medical Sciences Beijing ChinaState Key Laboratory for Quality Ensurance and Sustainable Use of Dao‐di Herbs, Artemisinin Research Center, and Institute of Chinese Materia Medica China Academy of Chinese Medical Sciences Beijing ChinaState Key Laboratory for Quality Ensurance and Sustainable Use of Dao‐di Herbs, Artemisinin Research Center, and Institute of Chinese Materia Medica China Academy of Chinese Medical Sciences Beijing ChinaState Key Laboratory for Quality Ensurance and Sustainable Use of Dao‐di Herbs, Artemisinin Research Center, and Institute of Chinese Materia Medica China Academy of Chinese Medical Sciences Beijing ChinaState Key Laboratory for Quality Ensurance and Sustainable Use of Dao‐di Herbs, Artemisinin Research Center, and Institute of Chinese Materia Medica China Academy of Chinese Medical Sciences Beijing ChinaState Key Laboratory for Quality Ensurance and Sustainable Use of Dao‐di Herbs, Artemisinin Research Center, and Institute of Chinese Materia Medica China Academy of Chinese Medical Sciences Beijing ChinaState Key Laboratory for Quality Ensurance and Sustainable Use of Dao‐di Herbs, Artemisinin Research Center, and Institute of Chinese Materia Medica China Academy of Chinese Medical Sciences Beijing ChinaState Key Laboratory for Quality Ensurance and Sustainable Use of Dao‐di Herbs, Artemisinin Research Center, and Institute of Chinese Materia Medica China Academy of Chinese Medical Sciences Beijing ChinaState Key Laboratory for Quality Ensurance and Sustainable Use of Dao‐di Herbs, Artemisinin Research Center, and Institute of Chinese Materia Medica China Academy of Chinese Medical Sciences Beijing ChinaBeiJing Shijitan Hospitals Capital Medical University Beijing ChinaState Key Laboratory for Quality Ensurance and Sustainable Use of Dao‐di Herbs, Artemisinin Research Center, and Institute of Chinese Materia Medica China Academy of Chinese Medical Sciences Beijing ChinaDepartment of Traditional Chinese Medicine and School of Pharmaceutical Sciences, Guangdong Basic Research Center of Excellence for Integrated Traditional and Western Medicine for Qingzhi Diseases, Guangdong Provincial Key Laboratory of Chinese Medicine Pharmaceutics Southern Medical University Guangzhou Guangdong ChinaState Key Laboratory for Quality Ensurance and Sustainable Use of Dao‐di Herbs, Artemisinin Research Center, and Institute of Chinese Materia Medica China Academy of Chinese Medical Sciences Beijing ChinaABSTRACT The insufficient infiltration and functional inhibition of CD8+ T cells due to tumor microenvironment (TME) are considered enormous obstacles to anti‐tumor immunotherapy. Herein, a pH‐responsive core‐shell manganese phosphate nanomodulator co‐loading siPD‐L1 and Mn2+ into nanoparticles coated with hyaluronic acid was prepared, which was aimed at the bidirectional reprogramming the tumor microenvironment: (1) “Brakes off,” restoring CD8+ T cells function by siPD‐L1 knockdowning PD‐L1 expression of tumor cells; (2) “Step on the accelerator,” promoting CD8+ T cells infiltration in tumors tissue based on the multidimensional immune effects of Mn2+ (immunogenic cell death induced the enhancing cGAS‐STING pathway, the proliferation and maturation of relative immune cells). Additionally, this strategy could induce macrophage polarization and inhibit the regulatory T cells in tumor site. This work provided a manganese phosphate nanomodulator to reprogram the immune TME for an enhanced comprehensive anti‐tumor effect of triple negative breast cancer, which offers a robust method for tumor immunotherapy in future clinical applications.https://doi.org/10.1002/EXP.70009cancer immunotherapymanganese phosphate nanomodulatornanomedicine |
| spellingShingle | Fei Xia Yuqian Lu Zipeng Gong Qingchao Tu Shuntao Liang Chen Wang HaiLu Yao LinYing Zhong Yuanfeng Fu Pengbo Guo Yichong Hou Xinyu Zhou Li Zou Licheng Gan Weiqi Chen Jiawei Yan Junzhe Zhang Huanhuan Pang Yuqing Meng Qiaoli Shi Chen Pan Xiaomei Tao Jigang Wang Qingfeng Du Chong Qiu Cancer Immunotherapy Based on the Bidirectional Reprogramming of the Tumor Microenvironment by a “Brakes Off/ Step on the Accelerator” Core‐Shell Manganese Phosphate/siPD‐L1 Modulator Exploration cancer immunotherapy manganese phosphate nanomodulator nanomedicine |
| title | Cancer Immunotherapy Based on the Bidirectional Reprogramming of the Tumor Microenvironment by a “Brakes Off/ Step on the Accelerator” Core‐Shell Manganese Phosphate/siPD‐L1 Modulator |
| title_full | Cancer Immunotherapy Based on the Bidirectional Reprogramming of the Tumor Microenvironment by a “Brakes Off/ Step on the Accelerator” Core‐Shell Manganese Phosphate/siPD‐L1 Modulator |
| title_fullStr | Cancer Immunotherapy Based on the Bidirectional Reprogramming of the Tumor Microenvironment by a “Brakes Off/ Step on the Accelerator” Core‐Shell Manganese Phosphate/siPD‐L1 Modulator |
| title_full_unstemmed | Cancer Immunotherapy Based on the Bidirectional Reprogramming of the Tumor Microenvironment by a “Brakes Off/ Step on the Accelerator” Core‐Shell Manganese Phosphate/siPD‐L1 Modulator |
| title_short | Cancer Immunotherapy Based on the Bidirectional Reprogramming of the Tumor Microenvironment by a “Brakes Off/ Step on the Accelerator” Core‐Shell Manganese Phosphate/siPD‐L1 Modulator |
| title_sort | cancer immunotherapy based on the bidirectional reprogramming of the tumor microenvironment by a brakes off step on the accelerator core shell manganese phosphate sipd l1 modulator |
| topic | cancer immunotherapy manganese phosphate nanomodulator nanomedicine |
| url | https://doi.org/10.1002/EXP.70009 |
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