Deformable liposomal codelivery of vorinostat and simvastatin promotes antitumor responses through remodeling tumor microenvironment

doi:10.1039/d0bm01516d

	Deformable liposomal codelivery of vorinostat and simvastatin promotes antitumor responses through remodeling tumor microenvironment
	Tu, Bin 1,2; He, Yang 1,2; Chen, Binfan 1,2; Wang, Yonghui 1,2; Gao, Yanrong 1,2; Shi, Mingjie 1; Liu, Tuanbing 1; Asrorov, Akmal M.1,3; Huang, Yongzhuo 1,2,4,5
刊名	BIOMATERIALS SCIENCE
	2020-12-21
卷号	8 期号:24 页码:7166-7176
ISSN号	2047-4830
DOI	10.1039/d0bm01516d
通讯作者	Huang, Yongzhuo(yzhuang@simm.ac.cn)
英文摘要	The tumor microenvironment (TME) and its major component tumor-associated macrophages (TAM) play a pivotal role in the development of non-small cell lung cancer (NSCLC). An epigenetic drug-based combinatory therapeutic strategy was proposed and a deformable liposome system (D-Lipo) was developed for vorinostat and simvastatin codelivery for remodeling the TME. The application of deformable liposomes in systemic cancer drug delivery has been underexplored and its potential in cancer therapy is largely unknown. This work revealed that D-Lipo exhibited an enhanced intratumor infiltration ability. The proposed therapeutic strategy was characterized by a chemo-free regimen and TME remodeling function. D-Lipo efficiently inhibited the growth of the xenografted lung tumor. The anti-tumor mechanisms involved the repolarization of TAM from the M2 to M1 phenotype, anti-angiogenesis, and the consequent TME remodeling. As a result, the amounts of the anti-tumor M1 macrophages and the cytotoxic CD8(+) T cells increased, while the amounts of the pro-tumor M2 macrophages and regulatory T cells (Tregs) reduced. It provides a promising avenue for epigenetic drug-based combination therapy for treating solid tumors.
资助项目	NFSC[81925035] ; NFSC[81673382] ; NFSC[81521005] ; Strategic Priority Research Program of CAS[XDA12050307] ; National Special Project for Significant New Drugs Development[2018ZX09711002-010-002] ; Shanghai SciTech Innovation Initiative[19431903100] ; Shanghai Belt and Road Initiative Young Foreign Scientists Program[18430740800] ; Shanghai Collaborative Innovation Group of Early Diagnosis and Precise Treatment of Hemangiomas and Vascular Malformations[SSMU-ZDCX20180701] ; CAS PIFI fellowship
WOS关键词	CELL LUNG-CANCER ; LIPID-METABOLISM ; DELIVERY ; PATHWAY ; MACROPHAGES ; INHIBITION ; EXPRESSION ; RESISTANCE ; BRAIN ; VEGF
WOS研究方向	Materials Science
语种	英语
出版者	ROYAL SOC CHEMISTRY
WOS记录号	WOS:000600664500027
内容类型	期刊论文
源URL	[http://119.78.100.183/handle/2S10ELR8/296407]
专题	中国科学院上海药物研究所
通讯作者	Huang, Yongzhuo
作者单位	1.Chinese Acad Sci, State Key Lab Drug Res, Shanghai Inst Mat Med, 501 Haike Rd, Shanghai 201203, Peoples R China 2.Univ Chinese Acad Sci, Beijing 100049, Peoples R China 3.Acad Sci Uzbek, Inst Bioorgan Chem, 83 M Ulughbek St, Tashkent 100125, Uzbekistan 4.NAIPA Key Lab Qual Res & Evaluat Pharmaceut Excip, Shanghai 201203, Peoples R China 5.Chinese Acad Sci, Inst Drug Res & Dev, Zhongshan Branch, Zhongshan 528437, Peoples R China
推荐引用方式 GB/T 7714	Tu, Bin,He, Yang,Chen, Binfan,et al. Deformable liposomal codelivery of vorinostat and simvastatin promotes antitumor responses through remodeling tumor microenvironment[J]. BIOMATERIALS SCIENCE,2020,8(24):7166-7176.
APA	Tu, Bin.,He, Yang.,Chen, Binfan.,Wang, Yonghui.,Gao, Yanrong.,...&Huang, Yongzhuo.(2020).Deformable liposomal codelivery of vorinostat and simvastatin promotes antitumor responses through remodeling tumor microenvironment.BIOMATERIALS SCIENCE,8(24),7166-7176.
MLA	Tu, Bin,et al."Deformable liposomal codelivery of vorinostat and simvastatin promotes antitumor responses through remodeling tumor microenvironment".BIOMATERIALS SCIENCE 8.24(2020):7166-7176.