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| A Peritumorally Injected Immunomodulating Adjuvant Elicits Robust and Safe Metalloimmunotherapy against Solid Tumors | |
| Zhang, Lingxiao1; Zhao, Jing1; Hu, Xi1,2,3; Wang, Chenhan1,4; Jia, Yingbo5; Zhu, Chaojie1; Xie, Shangzhi1; Lee, Jiyoung1; Li, Fangyuan1,6; Ling, Daishun1,2,6 | |
| 2022-09-04 | |
| Source Publication | ADVANCED MATERIALS
 |
| ISSN | 0935-9648 |
| Pages | 12 |
| Abstract | Clinical immunotherapy of solid tumors elicits durable responses only in a minority of patients, largely due to the highly immunosuppressive tumor microenvironment (TME). Although rational combinations of vaccine adjuvants with inflammatory cytokines or immune agonists that relieve immunosuppression represent an appealing therapeutic strategy against solid tumors, there are unavoidable nonspecific toxicities due to the pleiotropy of cytokines and undesired activation of off-target cells. Herein, a Zn2+ doped layered double hydroxide (Zn-LDH) based immunomodulating adjuvant, which not only relieves immunosuppression but also elicits robust antitumor immunity, is reported. Peritumorally injected Zn-LDH sustainably neutralizes acidic TME and releases abundant Zn2+, promoting a pro-inflammatory network composed of M1-tumor-associated macrophages, cytotoxic T cells, and natural-killer cells. Moreover, the Zn-LDH internalized by tumor cells effectively disrupts endo-/lysosomes to block autophagy and induces mitochondrial damage, and the released Zn2+ activates the cGas-STING signaling pathway to induce immunogenic cell death, which further promotes the release of tumor-associated antigens to induce antigen-specific cytotoxic T lymphocytes. Unprecedentedly, merely injection of Zn-LDH adjuvant, without using any cytotoxic inflammatory cytokines or immune agonists, significantly inhibits the growth, recurrence, and metastasis of solid tumors in mice. This study provides a rational bottom-up design of potent adjuvant for cancer metalloimmunotherapy against solid tumors. |
| Keyword | immunogenic cell death layered double hydroxide nutritional metal ions tumor microenvironment vaccine adjuvants |
| DOI | 10.1002/adma.202206915 |
| Language | 英语 |
| WOS Keyword | CELL-DEATH ; CANCER ; P53 ; ACTIVATION ; IMMUNITY ; ZINC ; NANOPARTICLES ; INHIBITION ; STRATEGIES ; INDUCTION |
| Funding Project | National Natural Science Foundation of China[32071374] ; National Natural Science Foundation of China[32101123] ; National Natural Science Foundation of China[32000985] ; National Natural Science Foundation of China[81761148029] ; Program of Shanghai Academic Research Leader under the Science and Technology Innovation Action Plan[21XD1422100] ; Leading Talent of "Ten Thousand Plan"-National High-Level Talents Special Support Plan, One Belt and One Road International Cooperation Project from Key Research and Development Program of Zhejiang Province[2019C04024] ; Zhejiang Provincial Natural Science Foundation of China[LR22C100001] ; Zhejiang Provincial Natural Science Foundation of China[LQ21H300003] ; Innovative Research Team of High-Level Local Universities in Shanghai[SHSMU-ZDCX20210900] ; Zhejiang Province Medical and Health Science Research Project[2021KY666] ; Chinese Postdoctoral Science Foundation[2021M702816] |
| WOS Research Area | Chemistry ; Science & Technology - Other Topics ; Materials Science ; Physics |
| WOS Subject | Chemistry, Multidisciplinary ; Chemistry, Physical ; Nanoscience & Nanotechnology ; Materials Science, Multidisciplinary ; Physics, Applied ; Physics, Condensed Matter |
| Funding Organization | National Natural Science Foundation of China ; Program of Shanghai Academic Research Leader under the Science and Technology Innovation Action Plan ; Leading Talent of "Ten Thousand Plan"-National High-Level Talents Special Support Plan, One Belt and One Road International Cooperation Project from Key Research and Development Program of Zhejiang Province ; Zhejiang Provincial Natural Science Foundation of China ; Innovative Research Team of High-Level Local Universities in Shanghai ; Zhejiang Province Medical and Health Science Research Project ; Chinese Postdoctoral Science Foundation |
| WOS ID | WOS:000849591300001 |
| Publisher | WILEY-V C H VERLAG GMBH |
| Citation statistics | |
| Document Type | 期刊论文 |
| Identifier | http://ir.ipe.ac.cn/handle/122111/54577 |
| Collection | 中国科学院过程工程研究所 |
| Corresponding Author | Li, Fangyuan; Ling, Daishun |
| Affiliation | 1.Zhejiang Univ, Coll Pharmaceut Sci, Inst Pharmaceut, Hangzhou Inst Innovat Med, Hangzhou 310058, Peoples R China 2.Shanghai Jiao Tong Univ, Frontiers Sci Ctr Transformat Mol, Natl Ctr Translat Med, Sch Chem & Chem Engn,State Key Lab Oncogenes & Re, Shanghai 200240, Peoples R China 3.Zhejiang Univ, Affiliated Hosp 1, Dept Clin Pharm, Sch Med, Hangzhou 310003, Peoples R China 4.Nanjing Med Univ, Jiangsu Breast Dis Ctr, Affiliated Hosp 1, Nanjing 210029, Peoples R China 5.Chinese Acad Sci, Inst Proc Engn, State Key Lab Biochem Engn, Beijing 100190, Peoples R China 6.WLA Labs, Shanghai 201203, Peoples R China |
| Recommended Citation GB/T 7714 | Zhang, Lingxiao,Zhao, Jing,Hu, Xi,et al. A Peritumorally Injected Immunomodulating Adjuvant Elicits Robust and Safe Metalloimmunotherapy against Solid Tumors[J]. ADVANCED MATERIALS,2022:12. |
| APA | Zhang, Lingxiao.,Zhao, Jing.,Hu, Xi.,Wang, Chenhan.,Jia, Yingbo.,...&Ling, Daishun.(2022).A Peritumorally Injected Immunomodulating Adjuvant Elicits Robust and Safe Metalloimmunotherapy against Solid Tumors.ADVANCED MATERIALS,12. |
| MLA | Zhang, Lingxiao,et al."A Peritumorally Injected Immunomodulating Adjuvant Elicits Robust and Safe Metalloimmunotherapy against Solid Tumors".ADVANCED MATERIALS (2022):12. |
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