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Enhance Cancer Cell Recognition and Overcome Drug Resistance Using Hyaluronic Acid and alpha-Tocopheryl Succinate Based Multifunctional Nanoparticles
Liang, Desheng; Wang, Ai-ting; Yang, Zhen-zhen; Liu, Yu-jie; Qi, Xian-rong
关键词Multidrug Resistance Hyaluronic Acid Alpha-tocopheryl Succinate Nanoparticle Docetaxel
刊名MOLECULAR PHARMACEUTICS
2015-06-01
DOI10.1021/acs.molpharmaceut.5b00129
12期:6页:2189-2202
收录类别SCI
文章类型Article
WOS标题词Science & Technology
类目[WOS]Medicine, Research & Experimental ; Pharmacology & Pharmacy
研究领域[WOS]Research & Experimental Medicine ; Pharmacology & Pharmacy
关键词[WOS]Vitamin-e Analogs ; Multidrug-resistance ; Induced Apoptosis ; Polyethylene-glycol ; Breast-cancer ; Anticancer Agents ; Co-delivery ; Targeting Mitochondria ; Tumor Microenvironment ; Polymeric Micelles
英文摘要

Multidrug resistance (MDR) presents a clinical obstacle to cancer chemotherapy. The main purpose of this study was to evaluate the potential of a hyaluronic acid (HA) and alpha-tocopheryl succinate (alpha-TOS) based nanoparticle to enhance cancer cell recognition and overcome MDR, and to explore the underlying mechanisms. A multifunctional nanoparticle, HTTP-50 NP, consisted of HA-alpha-TOS (HT) conjugate and D-alpha-tocopheryl polyethylene glycol succinate (TPGS) with docetaxel loaded in its hydrophobic core. The promoted tumor cell recognition and accumulation, cytotoxicity, and mitochondria-specific apoptotic pathways for the HTTP-50 NP were confirmed in MCF-7/Adr cells (P-gp-overexpressing cancer model), indicating that the formulated DTX and the conjugated alpha-TOS in the HTTP-50 NP could synergistically circumvent the acquired and intrinsic MDR in MCF-7/Adr cells. In vivo investigation on the MCF-7/Adr xenografted nude mice models confirmed that HTTP-50 NP possessed much higher tumor tissue accumulation and exhibited pronouncedly enhanced antiresistance tumor efficacy with reduced systemic toxicity compared with HTTP-0 NP and Taxotere. The mechanisms of the multifunctional HTTP-50 NP to overcome MDR and enhance antiresistance efficacy may be contributed by CD44 receptor-targeted delivery and P-gp efflux inhibition, and meanwhile to maximize antitumor efficacy by synergism of DTX and mitocan of alpha-TOS killing tumor cells.

语种英语
WOS记录号WOS:000355637900048
通讯作者邮箱qixr@bjmu.edu.cn
项目编号2013CB932501 ; 81273454 ; 81473156 ; 7132113 ; 20130001110055
资助机构National key Basic Research Program ; NSFC ; Beijing NSF ; Doctoral Foundation of the Ministry of Education
引用统计
被引频次:39[WOS]   [WOS记录]     [WOS相关记录]
文献类型期刊论文
版本出版稿
条目标识符http://ir.bjmu.edu.cn/handle/400002259/61687
专题北京大学药学院_药剂学系
作者单位Peking Univ, State Key Lab Nat & Biomimet Drugs, Sch Pharmaceut Sci, Beijing 100191, Peoples R China
推荐引用方式
GB/T 7714
Liang, Desheng,Wang, Ai-ting,Yang, Zhen-zhen,et al. Enhance Cancer Cell Recognition and Overcome Drug Resistance Using Hyaluronic Acid and alpha-Tocopheryl Succinate Based Multifunctional Nanoparticles[J]. MOLECULAR PHARMACEUTICS,2015,12(6):2189-2202.
APA Liang, Desheng,Wang, Ai-ting,Yang, Zhen-zhen,Liu, Yu-jie,&Qi, Xian-rong.(2015).Enhance Cancer Cell Recognition and Overcome Drug Resistance Using Hyaluronic Acid and alpha-Tocopheryl Succinate Based Multifunctional Nanoparticles.MOLECULAR PHARMACEUTICS,12(6),2189-2202.
MLA Liang, Desheng,et al."Enhance Cancer Cell Recognition and Overcome Drug Resistance Using Hyaluronic Acid and alpha-Tocopheryl Succinate Based Multifunctional Nanoparticles".MOLECULAR PHARMACEUTICS 12.6(2015):2189-2202.
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