Remodeling Tumor-Associated Macrophages and Neovascularization Overcomes EGFR(T790M)-Associated Drug Resistance by PD-L1 Nanobody-Mediated Codelivery

doi:10.1002/smll.201802372

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	Remodeling Tumor-Associated Macrophages and Neovascularization Overcomes EGFR(T790M)-Associated Drug Resistance by PD-L1 Nanobody-Mediated Codelivery
	Yin, Weimin 2,4; Yu, Xiaolu 1,2; Kang, Xuejia 2,3; Zhao, Yuge 2,4; Zhao, Pengfei 2,4; Jin, Hongyue 1,2; Fu, Xuhong 2,4; Wan, Yakun 2; Peng, Chengyuan 2; Huang, Yongzhuo1,2
刊名	SMALL
	2018-11-22
卷号	14 期号:47
关键词	antiangiogenesis EGFR(T790M) mutation PD-L1 nanobody simvastatin tumor-associated macrophage
ISSN号	1613-6810
DOI	10.1002/smll.201802372
文献子类	Article
英文摘要	Precision medicine has made a significant breakthrough in the past decade. The most representative success is the molecular targeting therapy of epidermal growth factor receptor (EGFR) tyrosine kinase inhibitors (TKI) in non-small-cell lung cancer (NSCLC) with oncogenic drivers, approved by the US Food and Drug Administration (FDA) as first-line therapeutics for substituting chemotherapy. However, the rapidly developed TKI resistance invariably leads to unsustainable treatment. For example, gefitinib is the first choice for advanced NSCLC with EGFR mutation, but most patients would soon develop secondary EGFR(T790M) mutation and acquire gefitinib resistance. TKI resistance is a severe emergency issue to be solved in NSCLC, but there are a few investigations of nanomedicine reported to address this pressing problem. To overcome EGFR(T790M)-associated drug resistance, a novel delivery and therapeutic strategy is developed. A PD-L1 nanobody is identified, and first used as a targeting ligand for liposomal codelivery. It is found that simvastatin/gefitinib combination nanomedicine can remodel the tumor microenvironment (e.g., neovascularization regulation, M2-macrophage repolarization, and innate immunity), and display the effectiveness of reversing the gefitinib resistance and enhancing the EGFR(T790M)-mutated NSCLC treatment outcomes. The novel simvastatin-based nanomedicine provides a clinically translatable strategy for tackling the major problem in NSCLC treatment and demonstrates the promise of an old drug for new application.
资助项目	973 Program, China[2014CB931900] ; NFSC[81673382] ; NFSC[81422048] ; NFSC[81521005] ; Strategic Priority Research Program of CAS[XDA12050307] ; National Special Project for Significant New Drugs Development[2018ZX09711002-010-002] ; CAS Scientific Research and Equipment Development Project[YZ201437] ; Fudan-SIMM Joint Research Fund[FU-SIMM20174009]
WOS关键词	CELL LUNG-CANCER ; GROWTH-FACTOR ; POLARIZATION ; MECHANISMS ; HYPOXIA ; MICROENVIRONMENT ; ANGIOGENESIS ; EXPRESSION ; GENERATION ; SURVIVAL
WOS研究方向	Chemistry ; Science & Technology - Other Topics ; Materials Science ; Physics
语种	英语
出版者	WILEY-V C H VERLAG GMBH
WOS记录号	WOS:000451178100001
内容类型	期刊论文
源URL	[http://119.78.100.183/handle/2S10ELR8/279489]
专题	药物制剂研究中心中科院受体结构与功能重点实验室新药研究国家重点实验室
通讯作者	Wan, Yakun; Huang, Yongzhuo
作者单位	1.Univ Chinese Acad Sci, Beijing 100049, Peoples R China; 2.Chinese Acad Sci, State Key Lab Drug Res, Shanghai Inst Mat Med, Shanghai 201203, Peoples R China; 3.Guangzhou Univ Chinese Med, Inst Trop Med, Guangzhou 510405, Guangdong, Peoples R China 4.Nanchang Univ, Coll Pharm, 461 Bayi Rd, Nanchang 330006, Jiangxi, Peoples R China;
推荐引用方式 GB/T 7714	Yin, Weimin,Yu, Xiaolu,Kang, Xuejia,et al. Remodeling Tumor-Associated Macrophages and Neovascularization Overcomes EGFR(T790M)-Associated Drug Resistance by PD-L1 Nanobody-Mediated Codelivery[J]. SMALL,2018,14(47).
APA	Yin, Weimin.,Yu, Xiaolu.,Kang, Xuejia.,Zhao, Yuge.,Zhao, Pengfei.,...&Huang, Yongzhuo.(2018).Remodeling Tumor-Associated Macrophages and Neovascularization Overcomes EGFR(T790M)-Associated Drug Resistance by PD-L1 Nanobody-Mediated Codelivery.SMALL,14(47).
MLA	Yin, Weimin,et al."Remodeling Tumor-Associated Macrophages and Neovascularization Overcomes EGFR(T790M)-Associated Drug Resistance by PD-L1 Nanobody-Mediated Codelivery".SMALL 14.47(2018).