Acid-activatible micelleplex delivering siRNA-PD-L1 for improved cancer immunotherapy of CDK4/6 inhibition
文献类型：期刊论文
| 作者 | Gao, Jing1,2,3,4; Zhang, Hanwu1,2; Zhou, Fengqi1,2; Hou, Bo1,2; Chen, Meiwan5; Xie, Zhigang6; Yu, Haijun1,2
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| 刊名 | CHINESE CHEMICAL LETTERS
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| 出版日期 | 2021-06-01 |
| 卷号 | 32期号:6页码:1929-1936 |
| 关键词 | Cancer immunotherapy siRNA delivery Acid-activatible micelleplex CDK4 6 inhibitor PD-L1 knockdown |
| ISSN号 | 1001-8417 |
| DOI | 10.1016/j.cclet.2020.12.0091001-8417/ |
| 通讯作者 | Yu, Haijun(hjyu@simm.ac.cn) |
| 英文摘要 | Cyclin-dependent kinases 4 and 6 inhibitors (CDK4/6i) have been demonstrated to trigger antitumor immunity for tumor regression. However, the therapeutic performance of CDK4/6i-meadiated cancer immunotherapy was impaired by the immunosuppressive tumor microenvironment (ITM) due to overexpression of programmed death ligand 1 (PD-L1) on the surface of cancer cell membrane. To improve the immunotherapeutic performance of CDK4/6i, we herein developed endosomal acidactivatable micelleplex for siRNA delivery and PD-L1 knockdown in the tumor cells in vitro and in vivo. We further demonstrated that the combination of PD-L1 knockdown and CDK4/6 inhibition facilitated intratumoral infiltration of cytotoxic T lymphocytes (CTLs), and elicited protective immune response and efficiently suppressed tumor growth in vivo. This study revealed the importance of molecular design of the micelleplex for highly efficient siRNA delivery, which might provide a novel insight for RNAi-based cancer immunotherapy. (c) 2021 Chinese Chemical Society and Institute of Materia Medica, Chinese Academy of Medical Sciences. Published by Elsevier B.V. All rights reserved. |
| WOS关键词 | BREAST-CANCER ; IMMUNE ; CELLS ; NANOPARTICLES ; RESISTANCE |
| 资助项目 | National Natural Science Foundation of China[51873228] ; National Natural Science Foundation of China[31671024] ; Basic Research Program of Shenzhen[JCYJ20180227175420974] ; Science and Technology Development Fund, Macau SAR[083/2017/A2] ; Open Research Fund of State Key Laboratory of Polymer Physics and Chemistry, Changchun Institute of Applied Chemistry, Chinese Academy of Sciences |
| WOS研究方向 | Chemistry |
| 语种 | 英语 |
| WOS记录号 | WOS:000658340900016 |
| 出版者 | ELSEVIER SCIENCE INC |
| 源URL | [http://119.78.100.183/handle/2S10ELR8/297109]  |
| 专题 | 新药研究国家重点实验室 |
| 通讯作者 | Yu, Haijun |
| 作者单位 | 1.Chinese Acad Sci, State Key Lab Drug Res, Shanghai Inst Mat Med, Shanghai 201203, Peoples R China 2.Chinese Acad Sci, Ctr Pharmaceut, Shanghai Inst Mat Med, Shanghai 201203, Peoples R China 3.Tongji Univ, Sch Med, Shanghai Peoples Hosp 10, Ultrasound Res & Educ Inst,Canc Ctr,Dept Med Ultr, Shanghai 200072, Peoples R China 4.Peking Univ Shenzhen Inst, Shenzhen 518055, Peoples R China 5.Univ Macau, Inst Chinese Med Sci, State Key Lab Qual Res Chinese Med, Macau 999078, Peoples R China 6.Chinese Acad Sci, Changchun Inst Appl Chem, State Key Lab Polymer Phys & Chem, Changchun 130022, Peoples R China |
| 推荐引用方式 GB/T 7714 | Gao, Jing,Zhang, Hanwu,Zhou, Fengqi,et al. Acid-activatible micelleplex delivering siRNA-PD-L1 for improved cancer immunotherapy of CDK4/6 inhibition[J]. CHINESE CHEMICAL LETTERS,2021,32(6):1929-1936. |
| APA | Gao, Jing.,Zhang, Hanwu.,Zhou, Fengqi.,Hou, Bo.,Chen, Meiwan.,...&Yu, Haijun.(2021).Acid-activatible micelleplex delivering siRNA-PD-L1 for improved cancer immunotherapy of CDK4/6 inhibition.CHINESE CHEMICAL LETTERS,32(6),1929-1936. |
| MLA | Gao, Jing,et al."Acid-activatible micelleplex delivering siRNA-PD-L1 for improved cancer immunotherapy of CDK4/6 inhibition".CHINESE CHEMICAL LETTERS 32.6(2021):1929-1936. |
入库方式： OAI收割
来源：上海药物研究所
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