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学科主题: 药学
题名:
LyP-1 Modification To Enhance Delivery of Artemisinin or Fluorescent Probe Loaded Polymeric Micelles to Highly Metastatic Tumor and Its Lymphatics
作者: Wang, Zhaohui; Yu, Yang; Ma, Jie2; Zhang, Haoran; Zhang, Hua; Wang, Xueqing; Wang, Jiancheng; Zhang, Xuan; Zhang, Qiang1
关键词: highly metastatic breast cancer ; tumor lymphatics ; specific delivery ; artemisinin ; polymeric micelles
刊名: MOLECULAR PHARMACEUTICS
发表日期: 2012-09-01
DOI: 10.1021/mp3002107
卷: 9, 期:9, 页:2646-2657
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]: BREAST-CANCER ; CONTROLLED-RELEASE ; HOMING PEPTIDE ; DRUG-RESISTANT ; CELLS ; NANOPARTICLES ; GROWTH ; PACLITAXEL ; LIPOSOMES ; LYMPHANGIOGENESIS
英文摘要:

Metastatic cancers are prone to form metastasis at a distance and acquire drug resistance, which are very common clinically and major obstacles to successful chemotherapy. Besides the tumor itself, the lymphatic system is increasingly emerging as a new target for anticancer therapy because it is an important route of tumor metastasis. To specifically deliver drug to both highly metastatic tumor and its lymphatics, tumor- and tumor lymphatics-homing peptide (LyP-1) conjugated PEG-PCL micelles (LyP-1-PM) were first constructed. Artemisinin (ART), a natural product with potential anticancer and antilymphangiogenesis effects, was chosen as the model drug and associated into the micelles. Both PM and LyP-1-PM had similar physiochemical properties, about 30 nm in size with uniform distribution. Highly metastatic breast cancer MDA-MB-435S cells and lymphatic endothelial cells (LEC) were applied as cell models. Flow cytometry and confocal microscopy studies showed that LyP-1-PM exhibited its specificity to both cell lines evidenced by its higher cellular uptake than PM. LyP-1-PM-ART demonstrated higher inhibition effect than PM-ART against these two cell lines in cell apoptosis, cell cycle and cytotoxicity tests. Near-infrared imaging showed that LyP-1-PM was distributed more in orthotopic MDA-MB-435S tumor than PM. Further study by colocalization indicated that PM accumulated near blood vessels, while LyP-1-PM further homed to tumor lymphatic vessels. LyP-1-PM achieved higher antitumor efficacy than other ART formulations in vivo with low toxicity. Both in vitro and in vivo studies here proved that LyP-1 modification enhanced the specific delivery of ART or fluorescent probe loaded polymeric micelles to MDA-MB-435S and LEC. Therefore, LyP-1-PM might be promising in terms of specific delivery of therapeutic or imaging agents to both highly metastatic breast tumor and its lymphatics.

语种: 英语
所属项目编号: 81130059 ; 2009CB930300 ; 2009ZX09310-001
项目资助者: National Science Foundation ; Ministry of Science and Technology of China
WOS记录号: WOS:000308263700028
Citation statistics:
内容类型: 期刊论文
URI标识: http://ir.bjmu.edu.cn/handle/400002259/61125
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, State Key Lab Nat & Biomimet Drugs, Beijing 100191, Peoples R China
2.Chinese Acad Med Sci, State Key Lab Mol Oncol, Canc Inst Hosp, Beijing 100021, Peoples R China

Recommended Citation:
Wang, Zhaohui,Yu, Yang,Ma, Jie,et al. LyP-1 Modification To Enhance Delivery of Artemisinin or Fluorescent Probe Loaded Polymeric Micelles to Highly Metastatic Tumor and Its Lymphatics[J]. MOLECULAR PHARMACEUTICS,2012,9(9):2646-2657.
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