中国科学院机构知识库网格
Chinese Academy of Sciences Institutional Repositories Grid
首页 机构 成果 学者
  
  1. CAS IR Grid
  2. 上海药物研究所
  3. 中国科学院上海药物研究所
  4. 新药研究国家重点实验室
Tumor-targeted PROTAC prodrug nanoplatform enables precise protein degradation and combination cancer therapy

文献类型：期刊论文

作者Zou, Zhi-feng5,6,7; Yang, Lei4,5,6; Nie, Hui-jun4; Gao, Jing5,6; Lei, Shu-min4; Lai, Yi5,6; Zhang, Fan3; Wagner, Ernst2; Yu, Hai-jun4,5,6; Chen, Xiao-hua1,4
刊名ACTA PHARMACOLOGICA SINICA
出版日期2024-04-12
页码12
关键词proteolysis-targeting chimeras tumor-targeted delivery precise protein degradation combination therapy triple-negative breast cancer
ISSN号1671-4083
DOI10.1038/s41401-024-01266-z
通讯作者Gao, Jing(jgao@simm.ac.cn) ; Yu, Hai-jun(hjyu@simm.ac.cn) ; Chen, Xiao-hua(xhchen@simm.ac.cn) ; Xu, Zhi-ai(zaxu@chem.ecnu.edu.cn)
英文摘要Proteolysis targeting chimeras (PROTACs) have emerged as revolutionary anticancer therapeutics that degrade disease-causing proteins. However, the anticancer performance of PROTACs is often impaired by their insufficient bioavailability, unsatisfactory tumor specificity and ability to induce acquired drug resistance. Herein, we propose a polymer-conjugated PROTAC prodrug platform for the tumor-targeted delivery of the most prevalent von Hippel-Lindau (VHL)- and cereblon (CRBN)-based PROTACs, as well as for the precise codelivery of a degrader and conventional small-molecule drugs. The self-assembling PROTAC prodrug nanoparticles (NPs) can specifically target and be activated inside tumor cells to release the free PROTAC for precise protein degradation. The PROTAC prodrug NPs caused more efficient regression of MDA-MB-231 breast tumors in a mouse model by degrading bromodomain-containing protein 4 (BRD4) or cyclin-dependent kinase 9 (CDK9) with decreased systemic toxicity. In addition, we demonstrated that the PROTAC prodrug NPs can serve as a versatile platform for the codelivery of a PROTAC and chemotherapeutics for enhanced anticancer efficiency and combination benefits. This study paves the way for utilizing tumor-targeted protein degradation for precise anticancer therapy and the effective combination treatment of complex diseases.
WOS关键词SQUAMOUS-CELL CARCINOMA ; HEPATOCELLULAR-CARCINOMA ; CONSTITUTIVE ACTIVATION ; SORAFENIB RESISTANCE ; IN-VITRO ; KAPPA-B ; STAT3 ; OLIGONUCLEOTIDES ; INHIBITION ; GROWTH
资助项目National Natural Science Foundation of China[22074043] ; National Natural Science Foundation of China[U22A20328] ; National Natural Science Foundation of China[22177120] ; Science and Technology Commission of Shanghai Municipality[20430711800] ; Science and Technology Commission of Shanghai Municipality[23ZR1475000] ; Sino German Workshop grant[W-0005] ; National Facility for Protein Science in Shanghai (NFPS), Shanghai Advanced Research Institute, CAS
WOS研究方向Chemistry ; Pharmacology & Pharmacy
语种英语
WOS记录号WOS:001201318400002
出版者NATURE PUBL GROUP
源URL[http://119.78.100.183/handle/2S10ELR8/310629]  
专题新药研究国家重点实验室
通讯作者Gao, Jing; Yu, Hai-jun; Chen, Xiao-hua; Xu, Zhi-ai
作者单位1.Univ Chinese Acad Sci, Hangzhou Inst Adv Study, Sch Pharmaceut Sci & Technol, Hangzhou 310024, Peoples R China
2.Ludwig Maximilians Univ Munchen, Dept Pharm, D-81377 Munich, Germany
3.Fudan Univ, Dept Chem, Shanghai 20043, Peoples R China
4.Nanjing Univ Chinese Med, Sch Chinese Mat Med, Nanjing 210023, Peoples R China
5.Chinese Acad Sci, Shanghai Inst Mat Med, Ctr Pharmaceut, Shanghai 201203, Peoples R China
6.Chinese Acad Sci, Shanghai Inst Mat Med, State Key Lab Drug Res, Shanghai 201203, Peoples R China
7.East China Normal Univ, Sch Chem & Mol Engn, Shanghai 200241, Peoples R China
推荐引用方式
GB/T 7714		 Zou, Zhi-feng,Yang, Lei,Nie, Hui-jun,et al. Tumor-targeted PROTAC prodrug nanoplatform enables precise protein degradation and combination cancer therapy[J]. ACTA PHARMACOLOGICA SINICA,2024:12.
APA Zou, Zhi-feng.,Yang, Lei.,Nie, Hui-jun.,Gao, Jing.,Lei, Shu-min.,...&Xu, Zhi-ai.(2024).Tumor-targeted PROTAC prodrug nanoplatform enables precise protein degradation and combination cancer therapy.ACTA PHARMACOLOGICA SINICA,12.
MLA Zou, Zhi-feng,et al."Tumor-targeted PROTAC prodrug nanoplatform enables precise protein degradation and combination cancer therapy".ACTA PHARMACOLOGICA SINICA (2024):12.

入库方式： OAI收割

来源：上海药物研究所

浏览0
下载0
收藏0
其他版本

除非特别说明，本系统中所有内容都受版权保护，并保留所有权利。