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学科主题药学
PSMA-mediated endosome escape-accelerating polymeric micelles for targeted therapy of prostate cancer and the real time tracing of their intracellular trafficking
Gao, Yajie1; Li, Yanfang2; Li, Yushu1; Yuan, Lan3; Zhou, Yanxia1; Li, Jinwen1; Zhao, Lei1; Zhang, Chao1; Li, Xinru1; Liu, Yan1
刊名NANOSCALE
2015
DOI10.1039/c4nr05738d
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
资助者National Natural Science Foundation of China ; National Key Science Research Program of China (973 Program) ; Ministry of Education ; National Natural Science Foundation of China ; National Key Science Research Program of China (973 Program) ; Ministry of Education
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
资助者National Natural Science Foundation of China ; National Key Science Research Program of China (973 Program) ; Ministry of Education ; National Natural Science Foundation of China ; National Key Science Research Program of China (973 Program) ; Ministry of Education
WOS记录号WOS:000347245500028
引用统计
被引频次:11[WOS]   [WOS记录]     [WOS相关记录]
文献类型期刊论文
条目标识符http://ir.bjmu.edu.cn/handle/400002259/66496
专题北京大学药学院_药剂学系
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
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GB/T 7714
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.
APA Gao, Yajie.,Li, Yanfang.,Li, Yushu.,Yuan, Lan.,Zhou, Yanxia.,...&Liu, Yan.(2015).PSMA-mediated endosome escape-accelerating polymeric micelles for targeted therapy of prostate cancer and the real time tracing of their intracellular trafficking.NANOSCALE,7(2),597-612.
MLA Gao, Yajie,et al."PSMA-mediated endosome escape-accelerating polymeric micelles for targeted therapy of prostate cancer and the real time tracing of their intracellular trafficking".NANOSCALE 7.2(2015):597-612.
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