Ternary Regulation of Tumor Microenvironment by Heparanase-Sensitive Micelle-Loaded Monocytes Improves Chemo-Immunotherapy of Metastatic Breast Cancer

doi:10.1002/adfm.202007402

	Ternary Regulation of Tumor Microenvironment by Heparanase-Sensitive Micelle-Loaded Monocytes Improves Chemo-Immunotherapy of Metastatic Breast Cancer
	Lang, Tianqun 1,2,3,4; Zheng, Zhong 1,2,5; Huang, Xin 1,2,4; Liu, Yiran 1,2; Zhai, Yihui 1,2,4; Zhang, Pengcheng 1,2,3,4; Li, Yaping 1,2,3,4,6; Yin, Qi 1,2,3,4
刊名	ADVANCED FUNCTIONAL MATERIALS
	2020-12-16
页码	12
关键词	breast cancer chemo-immunotherapy heparinase monocytes tumor environments
ISSN号	1616-301X
DOI	10.1002/adfm.202007402
通讯作者	Li, Yaping(ypli@simm.ac.cn) ; Yin, Qi(qyin@simm.ac.cn)
英文摘要	Tumor immunotherapy approaches such as programmed cell death-1/programmed cell death-ligand 1 (PD-1/PD-L1) checkpoint blockade and indoleamine 2,3-dioxygenase (IDO) inhibition are proven to promote immune response against tumors. Unfortunately, their positive response rates are unsatisfactory due to complicated immunosuppressive mechanisms in the tumor microenvironment, which can probably be rescued by integrating multiple immunoregulators and chemotherapeutic agents together. To improve the combination therapy of metastatic breast cancer, a ternary heparanase (Hpa)-sensitive micelle-loaded monocyte delivery system, termed as HDNH@MC, is designed, exploiting the capacity of Ly6C(hi) monocytes to be recruited to tumor sites and the overexpression of Hpa in tumors. The prodrugs of the chemotherapeutic agent docetaxel and IDO inhibitor NLG919 are synthesized by conjugating them on the substrate of Hpa, heparan sulfate. Then the PD-1/PD-L1 inhibitor HY19991-encapsulating prodrug micelle@Ly6C(hi) monocyte system is prepared. HNDH@MC elevates drug concentrations and relieves immunosuppression in tumors of 4T1 breast carcinomas mice model, thus enhancing the infiltration and activity of CD8(+) T cells and presenting significant anti-cancer effect. The lung metastasis is suppressed and the survival of mice is prolonged. HNDH@MC will be a promising option for treating metastatic breast cancer by synergy of tumor-targeting chemotherapy and immunotherapy.
资助项目	National Natural Science Foundation of China[81871471] ; National Natural Science Foundation of China[81630052] ; National Natural Science Foundation of China[81521005] ; National Natural Science Foundation of China[81690265] ; Natural Science Foundation of Shanghai[19ZR1479900] ; Key Scientific Research Program of CAS[QYZDJ-SSW-SMC020] ; International Partnership Program of CAS[153631KYSB20190013] ; SA-SIBS Scholarship Program
WOS关键词	IMMUNOGENIC CELL-DEATH ; DRUG-DELIVERY ; BURDEN RATIO ; EXPRESSION ; RECEPTOR ; DISTINCT
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:000598980900001
内容类型	期刊论文
源URL	[http://119.78.100.183/handle/2S10ELR8/296174]
专题	中国科学院上海药物研究所
通讯作者	Li, Yaping; Yin, Qi
作者单位	1.Chinese Acad Sci, Shanghai Inst Mat Med, State Key Lab Drug Res, 501 Haike Rd, Shanghai 201203, Peoples R China 2.Chinese Acad Sci, Shanghai Inst Mat Med, Ctr Pharmaceut, 501 Haike Rd, Shanghai 201203, Peoples R China 3.Yantai Inst Mat Med, Yantai Key Lab Nanomed & Adv Preparat, Yantai 264000, Peoples R China 4.Univ Chinese Acad Sci, Beijing 100049, Peoples R China 5.Jilin Univ, Coll Life Sci, Changchun 130012, Peoples R China 6.Yantai Univ, Sch Pharm, Yantai 264005, Peoples R China
推荐引用方式 GB/T 7714	Lang, Tianqun,Zheng, Zhong,Huang, Xin,et al. Ternary Regulation of Tumor Microenvironment by Heparanase-Sensitive Micelle-Loaded Monocytes Improves Chemo-Immunotherapy of Metastatic Breast Cancer[J]. ADVANCED FUNCTIONAL MATERIALS,2020:12.
APA	Lang, Tianqun.,Zheng, Zhong.,Huang, Xin.,Liu, Yiran.,Zhai, Yihui.,...&Yin, Qi.(2020).Ternary Regulation of Tumor Microenvironment by Heparanase-Sensitive Micelle-Loaded Monocytes Improves Chemo-Immunotherapy of Metastatic Breast Cancer.ADVANCED FUNCTIONAL MATERIALS,12.
MLA	Lang, Tianqun,et al."Ternary Regulation of Tumor Microenvironment by Heparanase-Sensitive Micelle-Loaded Monocytes Improves Chemo-Immunotherapy of Metastatic Breast Cancer".ADVANCED FUNCTIONAL MATERIALS (2020):12.