Dual-targeting biomimetic delivery for anti-glioma activity via remodeling the tumor microenvironment and directing macrophagemediated immunotherapy

doi:10.1039/c7sc04853j

CORC > 上海药物研究所 > 中国科学院上海药物研究所 > 药物制剂研究中心

	Dual-targeting biomimetic delivery for anti-glioma activity via remodeling the tumor microenvironment and directing macrophagemediated immunotherapy
	Zhao, Pengfei 1,3,4; Wang, Yonghui 1; Kang, Xuejia 1,2; Wu, Aihua 1,2; Yin, Weimin 1,3; Tang, Yisi 1,2; Wang, Jinyu 1; Zhang, Meng 1; Duan, Yifei 3; Huang, Yongzhuo1
刊名	CHEMICAL SCIENCE
	2018-03-14
卷号	9 期号:10 页码:2674-2689
ISSN号	2041-6520
DOI	10.1039/c7sc04853j
文献子类	Article
英文摘要	Tumor-associated macrophages (TAMs) are the major components in the tumor microenvironment (TME). The polarization from the protumor M2 (TAM2) to antitumor M1 (TAM1) phenotype can not only lift the immunosuppressive constraints and elicit cytotoxic T-cell immunity but also augment the chemotherapy efficacy. However, the treatment feasibility by TAM modulation in brain tumors and the mechanisms remained unknown. A dual-targeting biomimetic codelivery and treatment strategy was developed for anti-glioma activity. We demonstrated that the albumin nanoparticles modified with dual ligands, a transferrin receptor (TfR)-binding peptide T12 and mannose, efficiently passed through the BBB via the nutrient transporters (i.e., TfR and the albumin-binding receptor SPARC) that were both overexpressed in the BBB and glioma cells, thus achieving biomimetic delivery to glioma. Importantly, after penetrating the BBB, this system can take advantage of the overexpression of the SPARC and mannose receptors on TAM2, thus also targeting the protumor TAM2. With the codelivery disulfiram/copper complex and regorafenib, the system efficiently inhibited the glioma cell proliferation and successfully "re-educated" the protumor TAM2 towards antitumor TAM1. The treatment efficacy was examined in the gliomabearing nude mice and immunocompetent mice. It showed this system yielded an enhanced treatment outcome, owing to the synergistic combination of chemotherapy and macrophage-directed immunotherapy. The importance of this delivery and therapeutic strategy was to remodel the immune microenvironment and reprogram TAM and trigger macrophage-directed anti-glioma immunotherapy via the interplay of the TAM, Treg, and CD8(+) T cells and the effector cytokines. The albumin-based biomimetic brain delivery also provides a promising method for the pharmacotherapy of brain diseases.
资助项目	National Basic Research Program of China (973 Program)[2014CB931900] ; National Basic Research Program of China (973 Program)[2013CB932503] ; NSFC, China[81373357] ; NSFC, China[81422048] ; NSFC, China[81673382] ; NSFC, China[81521005] ; Strategic Priority Research Program of CAS, Personalized Medicines-Molecular Signature-based Drug Discovery and Development[XDA12050307] ; Fudan-SIMM Joint Research Fund[FU-SIMM20174009]
WOS关键词	REGULATORY T-CELLS ; BREAST-CANCER ; SOLID TUMORS ; DISULFIRAM ; GLIOBLASTOMA ; PROGRESSION ; METASTASIS ; DRUG ; THERAPY ; PROTEIN
WOS研究方向	Chemistry
语种	英语
出版者	ROYAL SOC CHEMISTRY
WOS记录号	WOS:000431100300004
内容类型	期刊论文
源URL	[http://119.78.100.183/handle/2S10ELR8/279852]
专题	药物制剂研究中心
通讯作者	Huang, Yongzhuo
作者单位	1.Chinese Acad Sci, Shanghai Inst Mat Med, 501 Haike Rd, Shanghai 201203, Peoples R China; 2.Guangzhou Univ, Chinese Med Trop Med Inst, 12 Jichang Rd, Guangzhou 501450, Guangdong, Peoples R China 3.Nanchang Univ, Coll Pharm, 461 Bayi Rd, Nanchang 330006, Jiangxi, Peoples R China; 4.Zhejiang Acad Med Sci, 182 Tianmushan Rd, Hangzhou 310013, Zhejiang, Peoples R China;
推荐引用方式 GB/T 7714	Zhao, Pengfei,Wang, Yonghui,Kang, Xuejia,et al. Dual-targeting biomimetic delivery for anti-glioma activity via remodeling the tumor microenvironment and directing macrophagemediated immunotherapy[J]. CHEMICAL SCIENCE,2018,9(10):2674-2689.
APA	Zhao, Pengfei.,Wang, Yonghui.,Kang, Xuejia.,Wu, Aihua.,Yin, Weimin.,...&Huang, Yongzhuo.(2018).Dual-targeting biomimetic delivery for anti-glioma activity via remodeling the tumor microenvironment and directing macrophagemediated immunotherapy.CHEMICAL SCIENCE,9(10),2674-2689.
MLA	Zhao, Pengfei,et al."Dual-targeting biomimetic delivery for anti-glioma activity via remodeling the tumor microenvironment and directing macrophagemediated immunotherapy".CHEMICAL SCIENCE 9.10(2018):2674-2689.