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Targeting extracellular DNA to deliver IGF-1 to the injured heart.

  • Author(s): Khan, Raffay;
  • Martinez, Mario;
  • Sy, Jay;
  • Pendergrass, Karl;
  • Che, Pao-lin;
  • Brown, Milton;
  • Cabigas, E;
  • Dasari, Madhuri;
  • Murthy, Niren;
  • Davis, Michael
  • et al.

Published Web Location

https://doi.org/10.1038/srep04257
Abstract

There is a great need for the development of therapeutic strategies that can target biomolecules to damaged myocardium. Necrosis of myocardium during a myocardial infarction (MI) is characterized by extracellular release of DNA, which can serve as a potential target for ischemic tissue. Hoechst, a histological stain that binds to double-stranded DNA can be conjugated to a variety of molecules. Insulin-like growth factor-1 (IGF-1), a small protein/polypeptide with a short circulating-half life is cardioprotective following MI but its clinical use is limited by poor delivery, as intra-myocardial injections have poor retention and chronic systemic presence has adverse side effects. Here, we present a novel delivery vehicle for IGF-1, via its conjugation to Hoechst for targeting infarcted tissue. Using a mouse model of ischemia-reperfusion, we demonstrate that intravenous delivery of Hoechst-IGF-1 results in activation of Akt, a downstream target of IGF-1 and protects from cardiac fibrosis and dysfunction following MI.

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