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通过血管内皮生长因子捕获修饰的扩增适配体自组装纳米结构抑制肿瘤生长和视网膜血管高通透性

Self-Assembled Nanoconstructs Modified with Amplified Aptamers Inhibited Tumor Growth and Retinal Vascular Hyperpermeability via Vascular Endothelial Growth Factor Capturing.

作者信息

Lee Jihyun, Lee Byung Joo, Lee Yeong Mi, Park Hansoo, Kim Jeong Hun, Kim Won Jong

机构信息

Center for Self-Assembly and Complexity, Institute for Basic Science (IBS) , Pohang 37673, Republic of Korea.

Department of Chemistry, Pohang University of Science and Technology (POSTECH) , Pohang 37673, Republic of Korea.

出版信息

Mol Pharm. 2017 May 1;14(5):1460-1468. doi: 10.1021/acs.molpharmaceut.6b00949. Epub 2017 Feb 22.

DOI:10.1021/acs.molpharmaceut.6b00949
PMID:28191845
Abstract

Here, nanoconstructs consisting of a DNA-amplified aptamer with a biocompatible polymer backbone for capturing target biomolecules are presented. First, the polymer-DNA nanoconstructs were prepared by hybridization of two complementary single-stranded DNAs that were each conjugated to a dextran polymer backbone. The designed polymer-DNA amplified aptamer nanoconstructs (PA-aNCs) were then prepared by utilizing polymer-DNA nanoconstructs conjugated with an aptamer (PA-NCs) using a rolling circle amplification reaction to amplify the aptamer. These PA-aNCs were successfully applied to alleviate tumor growth and vascular endothelial growth factor (VEGF)-induced retinal vascular hyperpermeability in vivo through the highly effective capture of human VEGF as a target molecule. These PA-aNCs could be used as therapeutic agent for anti-VEGF therapy by efficiently capturing human VEGF.

摘要

本文介绍了一种纳米构建体,其由具有生物相容性聚合物主链的DNA扩增适配体组成,用于捕获靶标生物分子。首先,通过将两条分别与葡聚糖聚合物主链偶联的互补单链DNA杂交来制备聚合物-DNA纳米构建体。然后,利用与适配体偶联的聚合物-DNA纳米构建体(PA-NCs),通过滚环扩增反应来扩增适配体,从而制备出设计好的聚合物-DNA扩增适配体纳米构建体(PA-aNCs)。这些PA-aNCs通过高效捕获人血管内皮生长因子(VEGF)作为靶标分子,成功地在体内减轻了肿瘤生长和VEGF诱导的视网膜血管高通透性。这些PA-aNCs可以通过有效捕获人VEGF用作抗VEGF治疗的治疗剂。

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