Shrapnel nanoparticles loading docetaxel inhibit metastasis and growth of breast cancer

doi:10.1016/j.biomaterials.2015.06.017

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	Shrapnel nanoparticles loading docetaxel inhibit metastasis and growth of breast cancer
	Xu, Pengfei 2,3; Meng, Qingshuo 2,3; Sun, Huiping 1,2,3; Yin, Qi2,3 ; Yu, Haijun2,3 ; Zhang, Zhiwen2,3 ; Cao, Mi 4; Zhang, Yingyi 4; Li, Yaping2,3
刊名	BIOMATERIALS
	2015-09
卷号	64 页码:10-20
关键词	Shrapnel Nanoparticles Breast cancer Metastasis Reduction-sensitive Enzyme-sensitive
ISSN号	0142-9612
DOI	10.1016/j.biomaterials.2015.06.017
文献子类	Article
英文摘要	Metastasis is one of the major obstacles for the successful therapy of breast cancer. To inhibit the metastasis and growth of breast cancer simultaneously, a new docetaxel (DTX) loaded shrapnel nano delivery system with the reduction- and enzyme-sensitive properties was designed and developed. Firstly, methoxy polyethylene glycol-peptide-vitamin E succinate (PPV), a matrix metalloproteinases (MMPs)-sensitive copolymer, was synthesized by conjugating mPEG and vitamin E succinate (VES) using an enzyme-sensitive peptide. Then, DTX loaded methoxy polyethylene glycol-s-s-vitamin E succinate (PSV) micelles (DPM) @ PPV-based liposomes (DPM@PL) were prepared by the incorporation of DPM into the PPV-based liposomes. DPM@PL showed a shrapnel structure with average particle size 113.3 +/- 2.7 nm. The drug loading and encapsulation efficiency of DPM@PL were 1.93% and 99.02%, respectively. An obvious burst release (>90%) of drug was observed in the simulated tumor microenvironment with MMPs and reductive glutathione. The cellular uptake and cytotoxicity of DPM@PL in 4T1 cells were significantly enhanced after the pre-treatment of activated MMP-9. Compared with Taxotere (R), DPM@PL remarkably increased the distribution of DTX in lung and tumor of 4T1 tumor-bearing mice, and inhibited the in situ tumor growth and pulmonary metastasis formation effectively through the enhanced DTX-induced apoptosis and the reduced metastasis-promoting proteins expression. Compared with saline group, the inhibitory rates of DPM@PL against tumor volume and lung metastasis were about 81% and 92%, respectively, and it didn't produce the significant systemic toxicity. As a result, DPM@PL could be a promising nano delivery system for the successful therapy of breast cancer. (C) 2015 Elsevier Ltd. All rights reserved.
资助项目	National Basic Research Program of China[2013CB932704] ; National Basic Research Program of China[2013CB932503] ; National Natural Science Foundation of China[81270047] ; National Natural Science Foundation of China[81373359]
WOS关键词	BIOMEDICAL APPLICATIONS ; POLYMERIC MICELLES ; DELIVERY ; INVASION ; THERAPY ; CELL ; BIODISTRIBUTION ; ANGIOGENESIS ; TUMORS ; SILICA
WOS研究方向	Engineering ; Materials Science
语种	英语
出版者	ELSEVIER SCI LTD
WOS记录号	WOS:000358631300003
内容类型	期刊论文
源URL	[http://119.78.100.183/handle/2S10ELR8/276428]
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	Yin, Qi
作者单位	1.Shenyang Pharmaceut Univ, Sch Pharm, Shenyang 110016, 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.Chinese Acad Sci, Shanghai Inst Biol Sci, Inst Biochem & Cell Biol, Natl Ctr Prot Sci Shanghai, Shanghai 201210, Peoples R China
推荐引用方式 GB/T 7714	Xu, Pengfei,Meng, Qingshuo,Sun, Huiping,et al. Shrapnel nanoparticles loading docetaxel inhibit metastasis and growth of breast cancer[J]. BIOMATERIALS,2015,64:10-20.
APA	Xu, Pengfei.,Meng, Qingshuo.,Sun, Huiping.,Yin, Qi.,Yu, Haijun.,...&Li, Yaping.(2015).Shrapnel nanoparticles loading docetaxel inhibit metastasis and growth of breast cancer.BIOMATERIALS,64,10-20.
MLA	Xu, Pengfei,et al."Shrapnel nanoparticles loading docetaxel inhibit metastasis and growth of breast cancer".BIOMATERIALS 64(2015):10-20.