Treatment of Malignant Brain Tumor by Tumor-Triggered Programmed Wormlike Micelles with Precise Targeting and Deep Penetration

doi:10.1002/adfm.201600642

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

	Treatment of Malignant Brain Tumor by Tumor-Triggered Programmed Wormlike Micelles with Precise Targeting and Deep Penetration
	Zeng, Lijuan 2,3,4; Zou, Lili 1,2,3; Yu, Haijun2,3 ; He, Xinyu 2,3; Cao, Haiqiang 2,3; Zhang, Zhiwen2,3 ; Yin, Qi2,3 ; Zhang, Pengcheng2,3 ; Gu, Wangwen2,3 ; Chen, Lingli2,3
刊名	ADVANCED FUNCTIONAL MATERIALS
	2016-06-20
卷号	26 期号:23 页码:4201-4212
ISSN号	1616-301X
DOI	10.1002/adfm.201600642
文献子类	Article
英文摘要	The efficient and specific drug delivery to brain tumor is a crucial challenge for successful systemic chemotherapy. To overcome these limitations, here a tumor-triggered programmed wormlike micelle is reported with precise targeting and deep penetration to treat malignant gliomas, which is composed of pH-responsive mPEG-b-PDPA copolymer and bioreducible cyclic RGD peptide targeted cytotoxic emtansine (DM1) conjugates (RGD-DM1). The RGD-DM1 loaded nanoscaled wormlike micelles (RNW) exhibit nanometer-sized wormlike assemblies with the transverse diameter of 21.3 +/- 1.8 nm and length within 60-600 nm, and the RGD targeting peptide in RNW is 4.2% in weight. RNW can be dissociated at intracellular acidic environments to release RGD-DM1, and be further degraded into DM1 by cleavage of disulfide bonds in the reductive milieu. In particular, by exploiting the unique wormlike structure and the RGD targeting peptide modification, RNW can be endowed with obviously enhanced drug delivery to brain, precise targeting to brain tumor, deep penetration into tumor mass, and efficient internalization into glioma cells in a programmed manner, thereby surprisingly leading to an 88.9% inhibition on tumor progression in an orthotopic brain tumor model. Therefore, the properly designed RNW can provide a promising delivery platform for systemic chemotherapy of brain tumor.
资助项目	National Basic Research Program of China[2015CB932103] ; National Basic Research Program of China[2013CB932503] ; National Natural Science Foundation of China[81270047] ; National Natural Science Foundation of China[81521005] ; K.C. Wong Education Foundation[00000000]
WOS关键词	DRUG-DELIVERY ; BREAST-CANCER ; LUNG METASTASIS ; NANOPARTICLES ; GLIOBLASTOMA ; THERAPY ; BARRIER ; GLIOMAS ; EFFICACY ; PRODRUG
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:000379731500017
内容类型	期刊论文
源URL	[http://119.78.100.183/handle/2S10ELR8/275992]
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	Zhang, Zhiwen; Li, Yaping
作者单位	1.Shanghai Jiao Tong Univ, Sch Pharm, Shanghai 200240, Peoples R China 2.Chinese Acad Sci, State Key Lab Drug Res, Shanghai 201203, Peoples R China; 3.Chinese Acad Sci, Shanghai Inst Mat Med, Ctr Pharmaceut, Shanghai 201203, Peoples R China; 4.Shenyang Pharmaceut Univ, Sch Pharm, Shenyang 110016, Peoples R China;
推荐引用方式 GB/T 7714	Zeng, Lijuan,Zou, Lili,Yu, Haijun,et al. Treatment of Malignant Brain Tumor by Tumor-Triggered Programmed Wormlike Micelles with Precise Targeting and Deep Penetration[J]. ADVANCED FUNCTIONAL MATERIALS,2016,26(23):4201-4212.
APA	Zeng, Lijuan.,Zou, Lili.,Yu, Haijun.,He, Xinyu.,Cao, Haiqiang.,...&Li, Yaping.(2016).Treatment of Malignant Brain Tumor by Tumor-Triggered Programmed Wormlike Micelles with Precise Targeting and Deep Penetration.ADVANCED FUNCTIONAL MATERIALS,26(23),4201-4212.
MLA	Zeng, Lijuan,et al."Treatment of Malignant Brain Tumor by Tumor-Triggered Programmed Wormlike Micelles with Precise Targeting and Deep Penetration".ADVANCED FUNCTIONAL MATERIALS 26.23(2016):4201-4212.