| 项目编号 |
PRJCA026217 |
| 项目标题 |
Intermetallics Induced Pyroptosis and Disulfidptosis Co-activated Tumor Immunotherapy in SLC7A11 High Expression Cancer |
| 涉及领域 |
Medical |
| 数据类型 |
Transcriptome or Gene expression
|
| 物种名称 |
Mus
|
| 描述信息 |
Pyroptosis, an immunogenic programmed cell death, could efficiently activate tumor immunogenicity and reprogram immunosuppressive microenvironment for boosting cancer immunotherapy. However, the overexpression of SLC7A11 promotes glutathione biosynthesis for maintaining redox balance and countering pyroptosis. Herein, we develop intermetallics modified with glucose oxidase (GOx) as pyroptosis promoter (Pd2Sn@GOx-SP), that not only induces pyroptosis through cascade biocatalysis for facilitating the immunogenicity of tumor and remodels tumor microenvironment, but also triggers disulfidptosis mediated by cystine accumulation to further promote pyroptosis. Experiments and DFT calculation show that the Pd2Sn nanorods (NRs) with maximum specific surface area exhibit stronger photothermal and enzyme catalytic activity compared with the other three morphologies. The peroxidase-mimic and oxidase-mimic activities of Pd2Sn NRs cause potent reactive oxygen species (ROS) storms for triggering pyroptosis, which could achieve self-reinforced by the photothermal effect, H2O2 supply accompanied by glycometabolism, and O2 production from the catalase-mimic activity of Pd2Sn NRs. Moreover, the increase of NADP+/NADPH ratio induced by glucose starvation could pose excessive cystine accumulation and inhibit glutathione synthesis, which could cause disulfidptosis and further augment ROS-mediated pyroptosis, respectively. This two-pronged treatment strategy could significantly play the therapeutic potency in improving the immune TME, providing a new perspective on expanding antitumor immunotherapy. |
| 样品范围 |
Monoisolate |
| 发布日期 |
2024-08-27 |
| 出版信息 |
| PubMed ID |
文章标题 |
杂志名称 |
Doi |
发表年份 |
| 39379392
|
Intermetallics triggering pyroptosis and disulfidptosis in cancer cells promote anti-tumor immunity
|
Nature Communications
|
10.1038/s41467-024-53135-2
|
2024
|
|
|
| 项目资金来源 |
| 机构 |
项目类型 |
授权项目ID |
授权项目名称 |
| Financial support from the National Natural Science Foundation of China
|
|
NSFC52002091
|
|
| Financial support from the National Natural Science Foundation of China
|
|
NSFC22205048
|
|
| Financial support from the National Natural Science Foundation of China
|
|
NSFC51972075
|
|
| Natural Science Foundation of Heilongjiang Provincial Government
|
|
LH2022H067
|
|
| Heilongjiang Natural Science Foundation Project of Outstanding Youth Project
|
|
YQ2023B005
|
|
| China Postdoctoral Science Foundation
|
|
2023TQ0091
|
|
| China Postdoctoral Science Foundation
|
|
2023T160154
|
|
| Heilongjiang Postdoctoral Fund
|
|
LBH-Z23014
|
|
| National Natural Science Foundation of China (NSFC)
|
|
No.U22A20316
|
|
| Ph.D. Student Research and Innovation Fund of the Fundamental Research Funds for the Central Universities
|
|
3072023GIP1002
|
|
| the Fundamental Research Funds for the Central Universities
|
|
N/A
|
|
|
|
| 提交者 |
Yang
Zhou (zhouyang@hrbmu.edu.cn)
|
| 提交单位 |
Harbin Medical University Cancer Hospital |
| 提交日期 |
2024-05-16 |
