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学科主题: 药学
题名:
Antitumor effect of iRGD-modified liposomes containing conjugated linoleic acid-paclitaxel (CLA-PTX) on B16-F10 melanoma
作者: Du, Ruo1; Zhong, Ting1; Zhang, Wei-Qiang1; Song, Ping1; Song, Wen-Ding1; Zhao, Yang1; Chao-Wang1; Tang, Yi-Qun3; Zhang, Xuan1,2; Zhang, Qiang1,2
关键词: peptide-modified liposome ; iRGD ; CLA-PTX ; antitumor effect ; in vitro ; in vivo
刊名: INTERNATIONAL JOURNAL OF NANOMEDICINE
发表日期: 2014
DOI: 10.2147/IJN.S65664
卷: 9, 页:3091-+
收录类别: SCI
文章类型: Article
WOS标题词: Science & Technology
类目[WOS]: Nanoscience & Nanotechnology ; Pharmacology & Pharmacy
研究领域[WOS]: Science & Technology - Other Topics ; Pharmacology & Pharmacy
关键词[WOS]: MOLECULAR-WEIGHT PROTAMINE ; DRUG-DELIVERY ; IN-VITRO ; FUNCTIONALIZED NANOPARTICLES ; DOXORUBICIN DELIVERY ; SOLID TUMORS ; EFFICACY ; ENDOCYTOSIS ; PRODRUGS ; THERAPY
英文摘要:

In the present study, we prepared a novel delivery system of iRGD (CRGDK/RGPD/EC)-modified sterically stabilized liposomes (SSLs) containing conjugated linoleic acid-paclitaxel (CLA-PTX). The anti-tumor effect of iRGD-SSL-CLA-PTX was investigated on B16-F10 melanoma in vitro and in vivo. The in vitro targeting effect of iRGD-modified SSLs was investigated in a real-time confocal microscopic analysis experiment. An endocytosis-inhibition assay was used to evaluate the endocytosis pathways of the iRGD-modified SSLs. In addition, the in vitro cellular uptake and in vitro cytotoxicity of iRGD-SSL-CLA-PTX were evaluated in B16-F10 melanoma cells. In vivo biodistribution and in vivo antitumor effects of iRGD-SSL-CLA-PTX were investigated in B16-F10 tumor-bearing mice. The induction of apoptosis by iRGD-SSL-CLA-PTX was evaluated in tumor-tissue sections. Real-time confocal microscopic analysis results indicated that the iRGD-modified SSLs internalized into B16-F10 cells faster than SSLs. The identified endocytosis pathway of iRGD-modified SSLs indicated that energy-and lipid raft-mediated endocytosis played a key role in the liposomes′ cellular uptake. The results of the cellular uptake experiment indicated that the increased cellular uptake of CLA-PTX in the iRGD-SSL-CLA-PTX-treated group was 1.9-, 2.4-, or 2.1-fold compared with that in the CLA-PTX group after a 2-, 4-, or 6-hour incubation, respectively. In the biodistribution test, the CLA-PTX level in tumor tissues from iRGD-SSL-CLA-PTX-treated mice at 1 hour (1.84 +/- 0.17 mu g/g) and 4 hours (1.17 +/- 0.28 mu g/g) was 2.3- and 2.0-fold higher than that of CLA-PTX solution at 1 hour (0.79 +/- 0.06 mu g/g) and 4 hours (0.58 +/- 0.04 mu g/g). The value of the area under the curve for the first 24 hours in the tumors of iRGD-SSL-CLA-PTX-treated mice was significantly higher than that in the SSL-CLA-PTX and CLA-PTX solution-treated groups (P<0.01). The in vivo antitumor results indicated that iRGD-SSL-CLA-PTX significantly inhibited the growth of B16-F10 tumors compared with the SSL-CLA-PTX or CLA-PTX solution-treatment groups (P<0.01). The results of tumor-cell apoptosis showed that tumors from the iRGD-SSL-CLA-PTX-treated group exhibited more advanced cell apoptosis compared with the control, CLA-PTX solution-, and SSL-CLA-PTX-treated groups. In conclusion, the antitumor effect of iRGD-SSL-CLA-PTX was confirmed on B16-F10 melanoma in vitro and in vivo.

语种: 英语
所属项目编号: 81172992 ; 2013CB932501 ; BMU20110263
项目资助者: National Natural Science Foundation of China ; National Basic Research Program of China (973 Program) ; Ministry of Education
WOS记录号: WOS:000338354700008
Citation statistics:
内容类型: 期刊论文
URI标识: http://ir.bjmu.edu.cn/handle/400002259/65373
Appears in Collections:北京大学药学院_药剂学系_期刊论文

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作者单位: 1.Peking Univ, Sch Pharmaceut Sci, Dept Pharmaceut, Beijing 100191, Peoples R China
2.Peking Univ, Sch Pharmaceut Sci, State Key Lab Nat & Biomimet Drugs, Beijing 100191, Peoples R China
3.China Pharmaceut Univ, Dept Clin Pharm, Nanjing, Jiangsu, Peoples R China

Recommended Citation:
Du, Ruo,Zhong, Ting,Zhang, Wei-Qiang,et al. Antitumor effect of iRGD-modified liposomes containing conjugated linoleic acid-paclitaxel (CLA-PTX) on B16-F10 melanoma[J]. INTERNATIONAL JOURNAL OF NANOMEDICINE,2014,9:3091-+.
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