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. 药物制剂研究中心
Reprogramming Tumor-Associated Macrophages To Reverse EGFR(T790M) Resistance by Dual-Targeting Codelivery of Gefitinib/Vorinostat

文献类型：期刊论文

作者Peng, Huige1,2; Chen, Binfan1,2; Huang, Wei1; Tang, Yubo1; Jiang, Yifan1; Zhang, Wenyuan1,2; Huang, Yongzhuo1
刊名NANO LETTERS
出版日期2017-12
卷号17期号:12页码:7684-7690
关键词Tumor-associated macrophages gefitinib vorinostat EGFR(T790M) nonsmall cell lung cancer drug resistance
ISSN号1530-6984
DOI10.1021/acs.nanolett.7b03756
文献子类Article
英文摘要Gefitinib is a first-line therapy in the EGFR-mutated nonsmall cell lung cancer (NSCLC). However, the development of drug resistance is almost unavoidable, thus leading to an unsustainable regimen. EGFR(T790M) mutation is the major cause responsible for the molecular-targeting therapy failure in NSCLC. Although the recently approved osimertinib is effective for the EGFR(T790M)-positive NSCLC, the osimertinib-resistant EGFR mutation is rapidly developed, too. In this study, we proposed a tumor-associated macrophage (TAM) reprogramming strategy for overcoming the EGFR(T790M)-massociated drug resistance via a dual-targeting codelivery system of gefitinib/vorinostat that acted on both TAM with overexpression of mannose receptors and the HER-2 positive NSCLC cells. The trastuzumab-modified, mannosylated liposomal system was able to repolarize the protumor M2 phenotype to the antitumor M1 and cause the elevating ROS in the cancer cells, consequently modulating the intracellular redox balance via ROS/NOX3/MsrA axis. The suppressed MsrA facilitated the EGFR(T790M) degradation through 790M oxidation by ROS, thus resensitizing the EGFR(T790M)-positive cells to gefitinib. The dual-targeting codelivery and TAM-reprogramming strategies provided a potential method for rescuing the EGFR(T790M)-caused resistance to tyrosine kinase inhibitor treatment.
WOS关键词CELL LUNG-CANCER ; DRUG-RESISTANCE ; T790M MUTATION ; EGFR T790M ; MICROENVIRONMENT ; OXIDATION
资助项目National Basic Research Program of China (973 Program)[2014CB931900] ; National Basic Research Program of China (973 Program)[2013CB932503] ; NSFC[81373357] ; NSFC[81422048] ; NSFC[81673382] ; NSFC[81521005] ; SIMM[CASIMM0120153023] ; CAS[YZ201437]
WOS研究方向Chemistry ; Science & Technology - Other Topics ; Materials Science ; Physics
语种英语
WOS记录号WOS:000418393300070
出版者AMER CHEMICAL SOC
源URL[http://119.78.100.183/handle/2S10ELR8/272367]  
专题药物制剂研究中心
通讯作者Huang, Yongzhuo
作者单位1.Chinese Acad Sci, Shanghai Inst Mat Med, Shanghai 201203, Peoples R China;
2.Univ Chinese Acad Sci, Beijing 100049, Peoples R China
推荐引用方式
GB/T 7714		 Peng, Huige,Chen, Binfan,Huang, Wei,et al. Reprogramming Tumor-Associated Macrophages To Reverse EGFR(T790M) Resistance by Dual-Targeting Codelivery of Gefitinib/Vorinostat[J]. NANO LETTERS,2017,17(12):7684-7690.
APA Peng, Huige.,Chen, Binfan.,Huang, Wei.,Tang, Yubo.,Jiang, Yifan.,...&Huang, Yongzhuo.(2017).Reprogramming Tumor-Associated Macrophages To Reverse EGFR(T790M) Resistance by Dual-Targeting Codelivery of Gefitinib/Vorinostat.NANO LETTERS,17(12),7684-7690.
MLA Peng, Huige,et al."Reprogramming Tumor-Associated Macrophages To Reverse EGFR(T790M) Resistance by Dual-Targeting Codelivery of Gefitinib/Vorinostat".NANO LETTERS 17.12(2017):7684-7690.

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。