Targeting extracellular DNA with a Hoechst-IGF-1 conjugate successfully delivers IGF-1 to infarcted myocardium, reducing fibrosis and preserving cardiac function in a preclinical model.
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Supports targeted IGF-1 delivery post-MI in preclinical models; leaves open human translation pending further studies.
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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Khan et al. (2014) studied Myocardial infarction. Hoechst-IGF-1 (H-IGF1) vs. PBS and Streptavidin-IGF1 (S-IGF1) was evaluated on Percent fractional shortening (%FS) at 28 days (p=<0.001).
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