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	P-gp inhibition and mitochondrial impairment by dual-functional nanostructure based on vitamin e derivatives to overcome multidrug resistance
	Tuguntaev, Ruslan G.1,2,3; Chen, Shizhu1,2,3,4; Eltahan, Ahmed Shaker1,2,3; Mozhi, Anbu2,3; Jin, Shubin5; Zhang, Jinchao4; Li, Chan1,2,3; Wang, Paul C.6,7; Liang, Xing-Jie1,2,3
刊名	Acs applied materials & interfaces
	2017-05-24
卷号	9期号:20页码:16901-16913
关键词	Vitamin e derivatives P-gp inhibition Multidrug resistance Mitochondrial impairment Drug delivery
ISSN号	1944-8244
DOI	10.1021/acsami.7b03877
通讯作者	Li, chan(lic@nanoctr.cn) ; Liang, xing-jie(liangxj@nanoctr.cn)
英文摘要	Vitamin e derivatives possess many essential features for drug-delivery applications, such as biocompatibility, stability, improvement of water solubility of hydrophobic compounds, anticancer activity, and the ability to overcome multidrug resistance (mdr). herein, vitamin e derivatives are used to overcome mdr through a combined p-glycoprotein (p-gp) inhibition and mitochondrial impairment strategy. a novel nanomicellar drug-delivery system as a carrier for doxorubicin (dox) was developed, in which d-alpha-tocopheryl polyethylene glycol 1000 succinate was used as a p-gp inhibitor, alpha-tocopheryl succinate was introduced as a mitochondrial disrupting agent, and d-alpha-tocopheryl polyethylene glycol 2000 succinate was used as the main building block of micelles. the optimal ratio between the components of the nanocarrier was determined. the resultant dox-loaded mixed micelles exhibited a suitable size of 52.08 nm, high drug-loading encapsulation efficiency (>98%), high stability, and ph-dependent drug release. in vitro experiments demonstrated a significantly increased cytotoxic activity of dox-loaded mixed micelles against resistant mcf-7/adr cells (45-fold higher than dox after 48 h of treatment). in vivo studies revealed superior antitumor efficiency with less cardio- and hepatotoxicities of dox-loaded micelles compared with that of free dox. these results highlight that the developed dox-loaded mixed micelles have a promising potential to overcome mdr in chemotherapy for clinical usage.
WOS关键词	ALPHA-TOCOPHERYL SUCCINATE ; DRUG-DELIVERY ; E TPGS ; CANCER-THERAPY ; MICELLES ; GLYCOPROTEIN ; DOXORUBICIN ; MECHANISM ; NANOPARTICLES ; CYTOTOXICITY
WOS研究方向	Science & Technology - Other Topics ; Materials Science
WOS类目	Nanoscience & Nanotechnology ; Materials Science, Multidisciplinary
语种	英语
出版者	AMER CHEMICAL SOC
WOS记录号	WOS:000402498600018
内容类型	期刊论文
URI标识	http://www.corc.org.cn/handle/1471x/2177391
专题	高能物理研究所
通讯作者	Li, Chan; Liang, Xing-Jie
作者单位	1.Chinese Acad Sci, Ctr Excellence Nanosci, 11 First North Rd, Beijing 100190, Peoples R China 2.Chinese Acad Sci, CAS Key Lab Biomed Effects Nanomat & Nanosafety, Lab Controllable Nanopharmaceut, Natl Ctr Nanosci & Technol, 11 First North Rd, Beijing 100190, Peoples R China 3.Univ Chinese Acad Sci, Beijing 100049, Peoples R China 4.Hebei Univ, Coll Chem & Environm Sci, Key Lab Med Chem & Mol Diag, Minist Educ,Chem Biol Key Lab Hebei Prov, Baoding 071002, Peoples R China 5.Beijing Municipal Inst Labour Protect, 55 Taoranting Rd, Beijing 100054, Peoples R China 6.Fu Jen Catholic Univ, Taipei 24205, Taiwan 7.Howard Univ, Dept Radiol, Lab Mol Imaging, Washington, DC 20060 USA
推荐引用方式 GB/T 7714	Tuguntaev, Ruslan G.,Chen, Shizhu,Eltahan, Ahmed Shaker,et al. P-gp inhibition and mitochondrial impairment by dual-functional nanostructure based on vitamin e derivatives to overcome multidrug resistance[J]. Acs applied materials & interfaces,2017,9(20):16901-16913.
APA	Tuguntaev, Ruslan G..,Chen, Shizhu.,Eltahan, Ahmed Shaker.,Mozhi, Anbu.,Jin, Shubin.,...&Liang, Xing-Jie.(2017).P-gp inhibition and mitochondrial impairment by dual-functional nanostructure based on vitamin e derivatives to overcome multidrug resistance.Acs applied materials & interfaces,9(20),16901-16913.
MLA	Tuguntaev, Ruslan G.,et al."P-gp inhibition and mitochondrial impairment by dual-functional nanostructure based on vitamin e derivatives to overcome multidrug resistance".Acs applied materials & interfaces 9.20(2017):16901-16913.

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