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Epigenetic-based combination therapy and liposomal codelivery overcomes osimertinib-resistant NSCLC via repolarizing tumor-associated macrophages

文献类型：期刊论文

作者Lin, Ting-ting4,5; Xiong, Wei2,3; Chen, Gui-hua3,4; He, Yang4; Long, Li4; Gao, Xin-fu5; Zhou, Jia-lin2; Lv, Wen-wen5; Huang, Yong-zhuo1,2,3,4
刊名ACTA PHARMACOLOGICA SINICA
出版日期2023-12-19
页码12
ISSN号1671-4083
关键词osimertinib resistance targeted drug delivery liposomes panobinostat tumor-associated macrophage combination therapy
DOI10.1038/s41401-023-01205-4
通讯作者Lv, Wen-wen(byyxlww@126.com) ; Huang, Yong-zhuo(yzhuang@simm.ac.cn)
英文摘要Osimertinib (Osi) is widely used as a first-line treatment for non-small cell lung cancer (NSCLC) with EGFR mutations. However, the majority of patients treated with Osi eventually relapse within a year. The mechanisms of Osi resistance remain largely unexplored, and efficient strategies to reverse the resistance are urgently needed. Here, we developed a lactoferrin-modified liposomal codelivery system for the combination therapy of Osi and panobinostat (Pan), an epigenetic regulator of histone acetylation. We demonstrated that the codelivery liposomes could efficiently repolarize tumor-associated macrophages (TAM) from the M2 to M1 phenotype and reverse the epithelial-mesenchymal transition (EMT)-associated drug resistance in the tumor cells, as well as suppress glycolysis, lactic acid production, and angiogenesis. Our results suggested that the combination therapy of Osi and Pan mediated by liposomal codelivery is a promising strategy for overcoming Osi resistance in NSCLC.
WOS关键词CELL LUNG-CANCER ; DRUG-RESISTANCE ; TRANSCRIPTIONAL REGULATION ; BRAIN METASTASIS ; LACTIC-ACID ; EGFR ; EGFR(T790M) ; EMT ; METABOLISM ; MECHANISMS
资助项目National Key Research and Development Program of China[2021YFC2400600] ; National Key Research and Development Program of China[2021YFE0103100] ; NFSC[81925035] ; Department of Science and Technology of Guangdong Province (High-level new RD institute)[2019B090904008] ; Department of Science and Technology of Guangdong Province (High-level new RD institute)[2021B0909050003] ; Scientific and Technological Innovation Leading Talent Project in Zhongshan City[LJ2021001] ; Scientific Research and Innovation Team Project in Zhongshan City[CXTD2022011] ; Research Foundation of Binzhou Medical University[BY2019KJ03]
WOS研究方向Chemistry ; Pharmacology & Pharmacy
语种英语
出版者NATURE PUBL GROUP
WOS记录号WOS:001126597400001
源URL[http://119.78.100.183/handle/2S10ELR8/308337]  
专题新药研究国家重点实验室
通讯作者Lv, Wen-wen; Huang, Yong-zhuo
作者单位1.NMPA Key Lab Qual Res & Evaluat Pharmaceut Excipie, Shanghai 201203, Peoples R China
2.Chinese Acad Sci, Zhongshan Inst Drug Discovery, Shanghai Inst Mat Med, Zhongshan 528437, Peoples R China
3.Guangzhou Univ Chinese Med, Artemisinin Res Ctr, Guangzhou 510450, Peoples R China
4.Chinese Acad Sci, Shanghai Inst Mat Med, State Key Lab Drug Res, Shanghai 201203, Peoples R China
5.Binzhou Med Univ Hosp, Dept Pharm, Binzhou 256603, Peoples R China
推荐引用方式
GB/T 7714		 Lin, Ting-ting,Xiong, Wei,Chen, Gui-hua,et al. Epigenetic-based combination therapy and liposomal codelivery overcomes osimertinib-resistant NSCLC via repolarizing tumor-associated macrophages[J]. ACTA PHARMACOLOGICA SINICA,2023:12.
APA Lin, Ting-ting.,Xiong, Wei.,Chen, Gui-hua.,He, Yang.,Long, Li.,...&Huang, Yong-zhuo.(2023).Epigenetic-based combination therapy and liposomal codelivery overcomes osimertinib-resistant NSCLC via repolarizing tumor-associated macrophages.ACTA PHARMACOLOGICA SINICA,12.
MLA Lin, Ting-ting,et al."Epigenetic-based combination therapy and liposomal codelivery overcomes osimertinib-resistant NSCLC via repolarizing tumor-associated macrophages".ACTA PHARMACOLOGICA SINICA (2023):12.

入库方式： OAI收割

来源：上海药物研究所

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