Engineering of Sono-Activatable Immunogels for Immunometabolism Disorder Normalization Therapy of Breast Cancer
文献类型：期刊论文
| 作者 | Guo, Yu7,8,9; Pan, Jiaxing6,7,8; Wang, Junjue5,7,8; Zhang, Huijuan7,8,9; Yang, Wenfang5,7,8; Chen, Fangmin7,8; Yin, Bowen9; Cai, Xiran4; Tao, Wei2,3; Lammers, Twan1 |
| 刊名 | JOURNAL OF THE AMERICAN CHEMICAL SOCIETY
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| 出版日期 | 2025-06-23 |
| 卷号 | 147期号:26页码:22412-22426 |
| ISSN号 | 0002-7863 |
| DOI | 10.1021/jacs.5c00124 |
| 英文摘要 | Sonodynamic therapy (SDT) represents a promising approach for localized immunotherapy of solid tumors, yet its clinical translation is limited by therapy stress-induced adaptive immune resistance. Here, we demonstrate that SDT initially elicits antitumor immune response while consequently induces immunometabolic dysregulation via the interferon-gamma (IFN-gamma)/indoleamine-2,3-dioxygenase-1 (IDO-1) axis to promote regulatory T cell (Treg) expansion. To counteract this negative regulation mechanism, we develop a sono-activatable prodrug (MB-MT) by conjugating the sonosensitizer methylene blue (MB) with the IDO-1 inhibitor 1-methyltryptophan (MT) via an ultrasound-labile urea bond. MB-MT is further incorporated into a thermosensitive hydrogel to yield an ultrasound-responsive immunogel that enables spatiotemporally confined SDT while locally suppressing IDO-1-mediated immune suppression. The combination of the immunogel with SDT treatment markedly normalizes the immunosuppressive tumor microenvironment to inhibit primary and metastatic tumor growth, and prevent postoperative recurrence in multiple synergistic mouse models of triple negative breast cancer (TNBC). This work presents a practical strategy for localized immunotherapy of TNBC by spatiotemporally confined normalization of immunometabolism disorder. |
| WOS关键词 | RESISTANCE |
| 资助项目 | National Natural Science Foundation of China[82203041] ; National Natural Science Foundation of China[W2412035] ; National Natural Science Foundation of China[U22A20328] ; National Natural Science Foundation of China[32411530049] ; National Natural Science Foundation of China[22474042] ; National Natural Science Foundation of China[24430713500] ; National Natural Science Foundation of China[23ZR1475000] ; National Natural Science Foundation of China[23490712700] ; Science and Technology Commission of Shanghai Municipality[BJKL2024046] ; Shanghai Oriental Talents Program[SKLDR-2023-KF-09] ; Open Funds of State Key Laboratory of Drug Research[B2022202029] ; Natural Science Foundation of Hebei Province ; SANOFI Scholarship Program ; National Facility for Protein Science in Shanghai (NFPS), Shanghai Advanced Research Institute, CAS ; Shanghai Institute of Materia Medica, CAS |
| WOS研究方向 | Chemistry |
| 语种 | 英语 |
| WOS记录号 | WOS:001516872300001 |
| 出版者 | AMER CHEMICAL SOC |
| 源URL | [http://119.78.100.183/handle/2S10ELR8/318681]  |
| 专题 | 新药研究国家重点实验室 |
| 通讯作者 | Lai, Yi; Yu, Haijun; Hu, Xiuli; Xu, Zhiai |
| 作者单位 | 1.RWTH Univ Hosp Aachen, Inst Expt Mol Imaging, Dept Nanomed & Theranost, D-52074 Aachen, Germany 2.Harvard Med Sch, Brigham & Womens Hosp, Dept Anesthesiol, Boston, MA 02115 USA 3.Harvard Med Sch, Ctr Nanomed, Boston, MA 02115 USA 4.ShanghaiTech Univ, Shanghai Engn Res Ctr Intelligent Vis & Imaging, Sch Informat Sci & Technol, Shanghai, Peoples R China 5.Nanjing Univ Chinese Med, Sch Chinese Mat Med, Nanjing 210023, Peoples R China 6.Shanghai Jiao Tong Univ, XinHua Hosp, Sch Med, Dept Gastroenterol, Shanghai, Peoples R China 7.Chinese Acad Sci, Shanghai Inst Mat Med, Ctr Pharmaceut, Shanghai 201203, Peoples R China 8.Chinese Acad Sci, Shanghai Inst Mat Med, Ctr Chem Biol, State Key Lab Drug Res, Shanghai 201203, Peoples R China 9.Hebei Univ Technol, Inst Polymer Sci & Engn, Sch Chem Engn, Tianjin 300130, Peoples R China |
| 推荐引用方式 GB/T 7714 | Guo, Yu,Pan, Jiaxing,Wang, Junjue,et al. Engineering of Sono-Activatable Immunogels for Immunometabolism Disorder Normalization Therapy of Breast Cancer[J]. JOURNAL OF THE AMERICAN CHEMICAL SOCIETY,2025,147(26):22412-22426. |
| APA | Guo, Yu.,Pan, Jiaxing.,Wang, Junjue.,Zhang, Huijuan.,Yang, Wenfang.,...&Xu, Zhiai.(2025).Engineering of Sono-Activatable Immunogels for Immunometabolism Disorder Normalization Therapy of Breast Cancer.JOURNAL OF THE AMERICAN CHEMICAL SOCIETY,147(26),22412-22426. |
| MLA | Guo, Yu,et al."Engineering of Sono-Activatable Immunogels for Immunometabolism Disorder Normalization Therapy of Breast Cancer".JOURNAL OF THE AMERICAN CHEMICAL SOCIETY 147.26(2025):22412-22426. |
入库方式： OAI收割
来源：上海药物研究所
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