Antiglioma via regulating oxidative stress and remodeling tumor-associated macrophage using lactoferrin-mediated biomimetic codelivery of simvastatin/fenretinide

doi:10.1016/j.jconrel.2018.08.012

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	Antiglioma via regulating oxidative stress and remodeling tumor-associated macrophage using lactoferrin-mediated biomimetic codelivery of simvastatin/fenretinide
	Mo, Xiaopeng 2,3; Zheng, Zening 1,3; He, Yang 3; Zhone, Huihai 2,3; Kane, Xuejia 1,3; Shi, Mingjie 3; Liu, Tuanbing 3; Jiao, Zheng 2; Huang, Yongzhuo3
刊名	JOURNAL OF CONTROLLED RELEASE
	2018-10-10
卷号	287 页码:12-23
关键词	Lactoferrin nanoparticle Reactive oxygen species Tumor-associated macrophages Brain-targeted delivery Biomimetic delivery Cell penetrating peptide Fenretinide Simvastatin
ISSN号	0168-3659
DOI	10.1016/j.jconrel.2018.08.012
文献子类	Article
英文摘要	Effective treatment of malignant glioma still remains a formidable challenge due to lack of the effective BBB-permeable drugs and efficient brain delivery methods, and the pharmacotherapy options are very limited. Therefore, to develop an effective therapeutic strategy is a pressing need. In this work, a noncytotoxic drug combination (i.e., simvastatin and fenretinide) was revealed to be potent for treating glioma, which was co-encapsulated into a TPGS-TAT-embedded lactoferrin nanoparticle system for achieving brain-targeted biomimetic delivery via the LRP-1 receptor. It was shown that the lactoferrin nanoparticle repolarized the tumor-associated macrophages from the M2 phenotype to M1 via regulating the STAT6 pathway, as well as induced the ROS-mediated mitochondrial apoptosis by inhibiting the Ras/Raf/p-Erk pathway in the glioma cells. The antiglioma efficacy was further demonstrated in both the subcutaneous and orthotopic glioma models. The repolarization of tumor-associated macrophages not only prompted the ROS generation but also induced the innate immunity (e.g., anti-tumor cytokine release). This delivery and therapeutic strategy provides a novel modality for the glioma treatment.
资助项目	973 Program, China[2014CB931900] ; NFSC[814022883] ; NFSC[81422048] ; NFSC[81673382] ; 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	RANDOMIZED PHASE-III ; JNK ACTIVATION ; CANCER-CELLS ; DELIVERY ; GLIOMA ; FENRETINIDE ; APOPTOSIS ; ROS ; MICROENVIRONMENT ; EPIDEMIOLOGY
WOS研究方向	Chemistry ; Pharmacology & Pharmacy
语种	英语
出版者	ELSEVIER SCIENCE BV
WOS记录号	WOS:000445127000002
内容类型	期刊论文
源URL	[http://119.78.100.183/handle/2S10ELR8/279535]
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	Huang, Yongzhuo
作者单位	1.Guangzhou Univ Chinese Med, Inst Trop Med, Guangzhou 510405, Guangdong, Peoples R China 2.Shanghai Univ, Coll Sci, Shanghai 200444, Peoples R China; 3.Chinese Acad Sci, Shanghai Inst Mat Med, State Key Lab Drug Res, 501 Haike Rd, Shanghai 201203, Peoples R China;
推荐引用方式 GB/T 7714	Mo, Xiaopeng,Zheng, Zening,He, Yang,et al. Antiglioma via regulating oxidative stress and remodeling tumor-associated macrophage using lactoferrin-mediated biomimetic codelivery of simvastatin/fenretinide[J]. JOURNAL OF CONTROLLED RELEASE,2018,287:12-23.
APA	Mo, Xiaopeng.,Zheng, Zening.,He, Yang.,Zhone, Huihai.,Kane, Xuejia.,...&Huang, Yongzhuo.(2018).Antiglioma via regulating oxidative stress and remodeling tumor-associated macrophage using lactoferrin-mediated biomimetic codelivery of simvastatin/fenretinide.JOURNAL OF CONTROLLED RELEASE,287,12-23.
MLA	Mo, Xiaopeng,et al."Antiglioma via regulating oxidative stress and remodeling tumor-associated macrophage using lactoferrin-mediated biomimetic codelivery of simvastatin/fenretinide".JOURNAL OF CONTROLLED RELEASE 287(2018):12-23.