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

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

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.

Keywords: DNA nanoconstructs; anti-VEGF therapy; antitumor therapy; polymer−DNA conjugates; retinal vascular hyperpermeability.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Aptamers, Nucleotide / chemistry*
  • DNA / chemistry*
  • Immunohistochemistry
  • Nanostructures / chemistry*
  • Polymers / chemistry*
  • Vascular Endothelial Growth Factor A / chemistry*

Substances

  • Aptamers, Nucleotide
  • Polymers
  • Vascular Endothelial Growth Factor A
  • DNA