| 项目编号 |
PRJCA034606 |
| 项目标题 |
Combining cisplatin and a STING agonist into one molecule for metalloimmunotherapy of cancer |
| 涉及领域 |
Medical |
| 数据类型 |
Single cell sequencing
|
| 物种名称 |
Mus musculus
|
| 描述信息 |
Mounting evidence suggests that strategies combining DNA-damaging agents and stimulator of interferon genes (STING) agonists are promising cancer therapeutic regimens because they can amplify STING activation and remodel the immunosuppressive tumor microenvironment. However, a single molecular entity comprising both agents has not yet been developed. Herein, we designed two PtIV-MSA-2 conjugates (I and II) containing the DNA-damaging chemotherapeutic drug cisplatin and the innate immuneactivating STING agonist MSA-2; these conjugates showed great potential as multispecific small-molecule drugs against pancreatic cancer. Mechanistic studies revealed that conjugate I upregulated the expression of transcripts associated with innate immunity and metabolism in cancer cells, significantly differing from cisplatin and MSA-2. An analysis of the tumor microenvironment demonstrated that conjugate I could enhance the infiltration of natural killer (NK) cells into tumors and promote the activation of T cells, NK cells and dendritic cells in tumor tissues. These findings indicated that conjugate I, which was created by incorporating a Pt chemotherapeutic drug and STING agonist into one molecule, is a promising and potent anticancer drug candidate, opening new avenues for small-molecule-based cancer metalloimmunotherapy |
| 样品范围 |
Single cell |
| 发布日期 |
2025-01-05 |
| 出版信息 |
| PubMed ID |
文章标题 |
杂志名称 |
Doi |
发表年份 |
| 38332843
|
Combining cisplatin and a STING agonist into one molecule for metalloimmunotherapy of cancer
|
National Science Review
|
10.1093/nsr/nwae020
|
2024
|
|
|
| 项目资金来源 |
| 机构 |
项目类型 |
授权项目ID |
授权项目名称 |
| Ministry of Science and Technology of the People's Republic of China (MOST)
|
National Key Technologies R&D Program
|
2019YFA0906600
|
|
|
|
| 提交者 |
Xinrui
Huang (652024240009@smail.nju.edu.cn)
|
| 提交单位 |
Nanjing University |
| 提交日期 |
2025-01-05 |
