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学科主题: 药学
题名:
Tumor-specific penetrating peptides-functionalized hyaluronic acid-D-alpha-tocopheryl succinate based nanoparticles for multi-task delivery to invasive cancers
作者: Liang, De-Sheng1,2; Su, Hai-Tao1,2; Liu, Yu-Jie1,2; Wang, Ai-Ting1,2; Qi, Xian-Rong1,2,3
关键词: Tumor-homing penetrating peptide tLyP-1 ; Site-specific delivery ; NRP-1 receptor ; CD44 receptor ; D-alpha-tocopheryl succinate (TOS)
刊名: BIOMATERIALS
发表日期: 2015-12-01
DOI: 10.1016/j.biomaterials.2015.08.035
卷: 71, 页:11-23
收录类别: SCI
文章类型: Article
WOS标题词: Science & Technology
类目[WOS]: Engineering, Biomedical ; Materials Science, Biomaterials
研究领域[WOS]: Engineering ; Materials Science
关键词[WOS]: DRUG-DELIVERY ; SOLID TUMORS ; MULTIFUNCTIONAL NANOPARTICLES ; THERAPEUTIC-EFFICACY ; ENDOTHELIAL-CELLS ; PROSTATE-CANCER ; GROWTH-FACTOR ; BRAIN GLIOMA ; IN-VIVO ; MICELLES
英文摘要:

Poor site-specific delivery and incapable deep-penetration into tumor are the intrinsic limitations to successful chemotherapy. Here, the tumor-homing penetrating peptide tLyP-1-functionalized nanoparticles (tLPTS/HATS NPs), composed of two modularized amphiphilic conjugates of tLyP-1-PEG-TOS (tLPTS) and TOS-grafted hyaluronic acid (HATS), had been fabricated for tumor-targeted delivery of docetaxel (DTX). The prepared tLPTS/HATS NPs had about 110 nm in mean diameter, high drug encapsulation efficiency (93%), and sustained drug release behavior. In vitro studies demonstrated that the tLPTS/HATS NPs exhibited enhanced intracellular delivery and much better anti-invasion ability, cytotoxicity, and apoptosis against both invasive PC-3 and MDA-MB-231 cells as compared to the non-tLyP-1-functionalized HATS NPs. The remarkable penetrability and inhibitory effect on both PC-3 and MDA-MB-231 multicellular tumor spheroids were also identified for the tLPTS/HATS NPs. In vivo biodistribution imaging demonstrated the tLPTS/HATS NPs possessed much more lasting accumulation and extensive distribution throughout tumor regions than the HATS NPs. The higher in vivo therapeutic efficacy with lower systemic toxicity of the tLPTS/HATS NPs was also verified by the PC-3 xenograft model in athymic nude mice. These results suggested that the designed novel tLPTS/HATS NPs were endowed with tumor recognition, internalization, penetration, and anti-invasion, and thus might be a promising anticancer drug delivery vehicle for targeted cancer therapy. (C) 2015 Elsevier Ltd. All rights reserved.

语种: 英语
所属项目编号: 81273454 ; 81473156 ; 2013CB932501 ; 7132113 ; 20130001110055
项目资助者: NSFC ; National key Basic Research Program ; Beijing NSF ; Doctoral Foundation of the Ministry of Education
WOS记录号: WOS:000362612800002
Citation statistics:
内容类型: 期刊论文
URI标识: http://ir.bjmu.edu.cn/handle/400002259/56775
Appears in Collections:北京大学药学院_期刊论文

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作者单位: 1.State Key Lab Nat & Biomimet Drugs, Beijing 100191, Peoples R China
2.Peking Univ, Sch Pharmaceut Sci, Beijing 100191, Peoples R China
3.Beijing Key Lab Mol Pharmaceut & New Drug Deliver, Beijing 100191, Peoples R China

Recommended Citation:
Liang, De-Sheng,Su, Hai-Tao,Liu, Yu-Jie,et al. Tumor-specific penetrating peptides-functionalized hyaluronic acid-D-alpha-tocopheryl succinate based nanoparticles for multi-task delivery to invasive cancers[J]. BIOMATERIALS,2015,71:11-23.
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