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学科主题: 药学
题名:
Enhance Cancer Cell Recognition and Overcome Drug Resistance Using Hyaluronic Acid and alpha-Tocopheryl Succinate Based Multifunctional Nanoparticles
作者: 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
发表日期: 2015-06-01
DOI: 10.1021/acs.molpharmaceut.5b00129
卷: 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
所属项目编号: 2013CB932501 ; 81273454 ; 81473156 ; 7132113 ; 20130001110055
项目资助者: National key Basic Research Program ; NSFC ; Beijing NSF ; Doctoral Foundation of the Ministry of Education
WOS记录号: WOS:000355637900048
Citation statistics:
内容类型: 期刊论文
URI标识: http://ir.bjmu.edu.cn/handle/400002259/61687
Appears in Collections:北京大学药学院_期刊论文

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作者单位: Peking Univ, State Key Lab Nat & Biomimet Drugs, Sch Pharmaceut Sci, Beijing 100191, Peoples R China

Recommended Citation:
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.
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