北京大学医学部机构知识库
Advanced  
IR@PKUHSC  > 北京大学药学院  > 药剂学系  > 期刊论文
学科主题: 药学
题名:
PSMA-mediated endosome escape-accelerating polymeric micelles for targeted therapy of prostate cancer and the real time tracing of their intracellular trafficking
作者: Gao, Yajie1; Li, Yanfang2; Li, Yushu1; Yuan, Lan3; Zhou, Yanxia1; Li, Jinwen1; Zhao, Lei1; Zhang, Chao1; Li, Xinru1; Liu, Yan1
刊名: NANOSCALE
发表日期: 2015
DOI: 10.1039/c4nr05738d
卷: 7, 期:2, 页:597-612
收录类别: SCI
文章类型: Article
WOS标题词: Science & Technology
类目[WOS]: Chemistry, Multidisciplinary ; Nanoscience & Nanotechnology ; Materials Science, Multidisciplinary ; Physics, Applied
研究领域[WOS]: Chemistry ; Science & Technology - Other Topics ; Materials Science ; Physics
关键词[WOS]: CELLULAR UPTAKE MECHANISM ; BLOCK-COPOLYMER MICELLES ; MEMBRANE ANTIGEN ; DRUG-DELIVERY ; IN-VITRO ; UNIMOLECULAR MICELLES ; MONOCLONAL-ANTIBODY ; ANTICANCER DRUG ; MULTIDRUG-RESISTANCE ; TRANSPORT MECHANISM
英文摘要:

The cytotoxicity of chemotherapeutic agents to healthy organs and drug resistance of tumor cells are believed to be the main obstacles to the successful cancer chemotherapy in the clinic. To ensure that anticancer drugs could be delivered to the tumor region, are quickly released from carriers in tumor cells and rapidly escape from endo/lysosomes, YPSMA-1-modified pH-sensitive polymeric micelles, which would be advantageous in recognizing the prostate specific membrane antigen (PSMA), were designed and fabricated for targeted delivery of paclitaxel to tumors based on the pH-sensitive diblock copolymer poly(2-ethyl-2-oxazoline)-poly(D,L-lactide) (PEOz-PLA) and YPSMA-1-PEOz-PLA for treating prostate cancer. HOOC-PEOz-PLA with a critical micelle concentration of 5.0 mg L-1 was synthesized and characterized by H-1 NMR and gel permeation chromatography. The prepared YPSMA-1-modified micelles, about 30 nm in diameter, exhibited a rapid release behavior at endo/lysosome pH and a favorable ability of fast endo/lysosome escape as observed by confocal microscopy. More importantly, we evidenced for the first time that both endosome and lysosome escape existed for pH-sensitive micelles via real time tracing using confocal microscopy, and the real time endo/lysosome escape process was also presented. The YPSMA-1-modified micelles were very effective in enhancing the cytotoxicity of paclitaxel by increasing the cellular uptake in PSMA-positive 22Rv1 cells, which was verified the correlation with PSMA expression in tumor cells by flow cytometric analysis and confocal microscopy. Moreover, the active targeting and pH-sensitivity endowed YPSMA-1-modified micelles with a higher antitumor efficacy and negligible systemic toxicity in 22Rv1 xenograft-bearing nude mice compared with unmodified micelles and Taxol (R). These results suggested that the application of combining YPSMA-1 modification with pH-sensitivity to polymeric micelles may be one approach in the efficient delivery of anticancer drugs for treating PSMA-positive prostate cancers.

语种: 英语
所属项目编号: 81172990 ; 2015CB932100 ; BMU20110263
项目资助者: National Natural Science Foundation of China ; National Key Science Research Program of China (973 Program) ; Ministry of Education
WOS记录号: WOS:000347245500028
Citation statistics:
内容类型: 期刊论文
URI标识: http://ir.bjmu.edu.cn/handle/400002259/66496
Appears in Collections:北京大学药学院_药剂学系_期刊论文

Files in This Item:

There are no files associated with this item.


作者单位: 1.Peking Univ, Sch Pharmaceut Sci, Dept Pharmaceut, Beijing 100191, Peoples R China
2.Peking Univ, Med & Hlth Analyt Ctr, Beijing 100191, Peoples R China
3.Peking Univ, Hosp 3, Cent Lab, Beijing 100191, Peoples R China

Recommended Citation:
Gao, Yajie,Li, Yanfang,Li, Yushu,et al. PSMA-mediated endosome escape-accelerating polymeric micelles for targeted therapy of prostate cancer and the real time tracing of their intracellular trafficking[J]. NANOSCALE,2015,7(2):597-612.
Service
Recommend this item
Sava as my favorate item
Show this item's statistics
Export Endnote File
Google Scholar
Similar articles in Google Scholar
[Gao, Yajie]'s Articles
[Li, Yanfang]'s Articles
[Li, Yushu]'s Articles
CSDL cross search
Similar articles in CSDL Cross Search
[Gao, Yajie]‘s Articles
[Li, Yanfang]‘s Articles
[Li, Yushu]‘s Articles
Related Copyright Policies
Null
Social Bookmarking
Add to CiteULike Add to Connotea Add to Del.icio.us Add to Digg Add to Reddit
所有评论 (0)
暂无评论
 
评注功能仅针对注册用户开放,请您登录
您对该条目有什么异议,请填写以下表单,管理员会尽快联系您。
内 容:
Email:  *
单位:
验证码:   刷新
您在IR的使用过程中有什么好的想法或者建议可以反馈给我们。
标 题:
 *
内 容:
Email:  *
验证码:   刷新

Items in IR are protected by copyright, with all rights reserved, unless otherwise indicated.

 

 

Valid XHTML 1.0!
Copyright © 2007-2017  北京大学医学部 - Feedback
Powered by CSpace