Low-molecular-weight protamine-modified PLGA nanoparticles for overcoming drug-resistant breast cancer

doi:10.1016/j.jconrel.2014.06.051

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	Low-molecular-weight protamine-modified PLGA nanoparticles for overcoming drug-resistant breast cancer
	Wang, Huixin 1,5; Zhao, Yongxing 1; Wang, Huiyuan; Gong, Junbo 2; He, Huining 3; Shin, Meong Cheol 4; Yang, Victor C.3,4; Huang, Yongzhuo5
刊名	JOURNAL OF CONTROLLED RELEASE
	2014-10-28
卷号	192 页码:47-56
关键词	Cell-penetrating peptide PLGA nanoparticle Doxorubicin Low-molecular-weight protamine Multidrug resistance Breast cancer
ISSN号	0168-3659
DOI	10.1016/j.jconrel.2014.06.051
文献子类	Article
英文摘要	Multidrug resistance (MDR) is a major challenge for cancer therapy. Herein, we report a simple yet effective system, cell-penetrating peptide (CPP)-assisted poly(lactic-co-glycolic acid nanoparticles (PLGA NPs), for improving doxorubicin (DOX) delivery and overcoming MDR cancer. We selected the naturally derived CPP low-molecular-weight protamine (LMWP) to modify PLGA NP for enhanced drug delivery. We demonstrated that multiple mechanisms ("synergistic multipronged delivery") were responsible for the anti-MDR effects of LMWP/PLGA NP. This delivery system could boost intracellular and intranuclear delivery, thereby circumventing drug efflux. Use of a P-glycoprotein inhibitor did not further increase the efficiency of intracellular delivery of LMWP/PLGA/DOX NP, suggesting that delivery of LMWP-based NP was not affected by transporter-mediated drug efflux. Importantly, enhanced uptake and penetration within the tumor was found in mice given LMWP-based NP. LMWP/PLGA NP effectively arrested tumor growth in mice harboring drug-resistant breast tumors, thereby improving treatment outcomes without detectable toxicities. These data suggest that our system could provide effective yet safe anti-MDR cancer therapy based on a synergistic, multipronged drug-delivery strategy. (C) 2014 Elsevier B.V. All rights reserved.
资助项目	National Basic Research Program of China (973 Program)[2013CB932503] ; National Basic Research Program of China (973 Program)[2014CB931902] ; NSFC, China[91029743] ; NSFC, China[81172996] ; NSFC, China[81373357] ; NSFC, China[81361140344] ; Chinese Postdoctoral Science Foundation[2012M510097] ; Chinese Postdoctoral Science Foundation[2013T60478] ; Shanghai Pu-jiang Scholar Program[11PJ1411800]
WOS关键词	MESOPOROUS SILICA NANOPARTICLES ; INTERSTITIAL FLUID PRESSURE ; MULTIDRUG-RESISTANCE ; DOXORUBICIN DELIVERY ; ANTICANCER DRUGS ; TUMOR-TISSUE ; SOLID TUMORS ; IN-VITRO ; PENETRATION ; PEPTIDE
WOS研究方向	Chemistry ; Pharmacology & Pharmacy
语种	英语
出版者	ELSEVIER SCIENCE BV
WOS记录号	WOS:000342460400006
内容类型	期刊论文
源URL	[http://119.78.100.183/handle/2S10ELR8/276866]
专题	药物制剂研究中心
通讯作者	Huang, Yongzhuo
作者单位	1.Zhengzhou Univ, Coll Pharmaceut Sci, Zhengzhou 450001, Peoples R China; 2.Tianjin Univ, Sch Chem Engn & Technol, Tianjin 300072, Peoples R China; 3.Tianjin Med Univ, Sch Pharm, Tianjin Key Lab Technol Enabling Dev Clin Therape, Tianjin 300070, Peoples R China; 4.Univ Michigan, Coll Pharm, Ann Arbor, MI 48109 USA 5.Chinese Acad Sci, Shanghai Inst Mat Med, Shanghai 201203, Peoples R China;
推荐引用方式 GB/T 7714	Wang, Huixin,Zhao, Yongxing,Wang, Huiyuan,et al. Low-molecular-weight protamine-modified PLGA nanoparticles for overcoming drug-resistant breast cancer[J]. JOURNAL OF CONTROLLED RELEASE,2014,192:47-56.
APA	Wang, Huixin.,Zhao, Yongxing.,Wang, Huiyuan.,Gong, Junbo.,He, Huining.,...&Huang, Yongzhuo.(2014).Low-molecular-weight protamine-modified PLGA nanoparticles for overcoming drug-resistant breast cancer.JOURNAL OF CONTROLLED RELEASE,192,47-56.
MLA	Wang, Huixin,et al."Low-molecular-weight protamine-modified PLGA nanoparticles for overcoming drug-resistant breast cancer".JOURNAL OF CONTROLLED RELEASE 192(2014):47-56.