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王均教授研究组在MOLECULAR PHARMACEUTICS上发表题为Targeted Delivery of Antisense...的论文

时间:2011-03-07 01:39:00 来源:合肥微尺度物质科学国家实验室|http://www.hfnl.ustc.edu.cn
  2011年,我室BIO-X交叉科学研究部王均教授研究组在MOLECULAR PHARMACEUTICS上发表题为Targeted Delivery of Antisense Inhibitor of miRNA for Antiangiogenesis Therapy Using cRGD-Functionalized Nanoparticles的论文。

Source: MOLECULAR PHARMACEUTICS Volume: 8 Issue: 1 Pages: 250-259 Published: JAN-FEB 2011

Liu XQ (Liu, Xi-Qiu)1, Song WJ (Song, Wen-Jing)1, Sun TM (Sun, Tian-Meng)2, Zhang PZ (Zhang, Pei-Zhuo)3, Wang J (Wang, Jun)1
Addresses:
1. Univ Sci & Technol China, Sch Life Sci, Key Lab Brain Funct & Dis, Chinese Acad Sci, Hefei 230027, Anhui Peoples R China
2. Univ Sci & Technol China, Hefei Natl Lab Phys Sci Microscale, Hefei 230027, Anhui Peoples R China
3. Suzhou GenePharma Co Ltd, Suzhou 215123, Jiangsu Peoples R China
E-mail Addresses: jwang699@ustc.edu.cn

Reprint Address: Wang, J (reprint author), Univ Sci & Technol China, Sch Life Sci, Key Lab Brain Funct & Dis, Chinese Acad Sci, Hefei 230027, Anhui Peoples R China

Abstract:
MiRNAs are viable therapeutic targets for cancer therapy, but the targeted delivery of miRNA or its anti-miRNA antisense oligonucleotides (AMOs) remains a challenge. We report here a PEGylated LPH (liposome-polycation-hyaluronic acid) nanoparticle formulation modified with cyclic RGD peptide (cRGD) for specific and efficient delivery of AMO into endothelial cells, targeting alpha(v)beta(3) integrin present on the tumor neovasculature. The nanoparticles effectively delivered anti-miR-296 AMO to the cytoplasm and downregulated the target miRNA in human umbilical vein endothelial cells (HUVECs), which further efficiently suppressed blood tube formulation and endothelial cell migration, owing to significant upregulation of hepatocyte growth factor-regulated tyrosine kinase substrate (HGS), whereas nanoparticles without cRGD modification showed only little AMO uptake and miRNA silencing activity. In vivo assessment of angiogenesis using Matrigel plug assay also demonstrated that cRGD modified LPH nanoparticles have potential for antiangiogenesis in miRNA therapeutics. With the delivery of anti-miR-296 AMO by targeted nanoparticles, significant decrease in microvessel formulation within Matrigel was achieved through suppressing the invasion of CD31-positive cells into Matrigel and prompting HGS expression in angiogenic endothelial cells.

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