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

文献类型：期刊论文

作者Lang, Tianqun2,3,4,5; Zheng, Zhong1,2,3; Huang, Xin2,3,5; Liu, Yiran2,3; Zhai, Yihui2,3,5; Zhang, Pengcheng2,3,4,5; Li, Yaping2,3,4,5,6; Yin, Qi2,3,4,5
刊名ADVANCED FUNCTIONAL MATERIALS
出版日期2020-12-16
页码12
ISSN号1616-301X
关键词breast cancer chemo-immunotherapy heparinase monocytes tumor environments
DOI10.1002/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.
WOS关键词IMMUNOGENIC CELL-DEATH ; DRUG-DELIVERY ; BURDEN RATIO ; EXPRESSION ; RECEPTOR ; DISTINCT
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
源URL[http://119.78.100.183/handle/2S10ELR8/296174]  
专题新药研究国家重点实验室
通讯作者Li, Yaping; Yin, Qi
作者单位1.Jilin Univ, Coll Life Sci, Changchun 130012, Peoples R China
2.Chinese Acad Sci, Shanghai Inst Mat Med, State Key Lab Drug Res, 501 Haike Rd, Shanghai 201203, Peoples R China
3.Chinese Acad Sci, Shanghai Inst Mat Med, Ctr Pharmaceut, 501 Haike Rd, Shanghai 201203, Peoples R China
4.Yantai Inst Mat Med, Yantai Key Lab Nanomed & Adv Preparat, Yantai 264000, Peoples R China
5.Univ Chinese Acad Sci, Beijing 100049, 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.

入库方式： OAI收割

来源：上海药物研究所

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