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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/srep04257Abstract
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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