Theranostic Nucleic Acid Binding Nanoprobe Exerts Anti-inflammatory and Cytoprotective Effects in Ischemic Injury.

Abstract

Extracellular nucleic acids are proinflammatory molecules that have been implicated in a diverse range of diseases. We report here the development of a multivalent nucleic acid scavenging nanoprobe, where the fluorochrome thiazole orange (TO) is conjugated to a polymeric 40 kDa dextran carrier. Dextran-TO (Dex-TO) has nanomolar affinity for mammalian and bacterial nucleic acids and attenuates the production of inflammatory cytokines from activated macrophages exposed to DNA and RNA. Mice with myocardial ischemia reperfusion that were treated with Dex-TO showed a decrease in myocardial macrophage infiltration at 24 hours (p<0.05) and a decrease in infarct size (18% ± 9%, p<0.01) on day 7. Dex-TO allows sites of injury to be identified with fluorescence imaging, while simultaneously exerting an anti-inflammatory and cytoprotective effect. Dex-TO could be of significant diagnostic and therapeutic (theranostic) utility in a broad range of conditions including ischemia, trauma, burns, sepsis and autoimmune disease.

• Authors: Howard H Chen, Hushan Yuan, Hoonsung Cho, Yan Feng, Soeun Ngoy, Anand T N Kumar, Ronglih Liao, Wei Chao, Lee Josephson, David E Sosnovik
• Journal: Theranostics (Theranostics) Vol. 7 Issue 4 Pg. 814-825 ( 2017) ISSN: 1838-7640 [Electronic] Australia
• PMID: 28382156 (Publication Type: Journal Article, Research Support, N.I.H., Extramural)

Chemical References

• Anti-Inflammatory Agents
• Benzothiazoles
• Dextrans
• Nucleic Acids
• Quinolines
• thiazole orange

Topics

• Animals
• Anti-Inflammatory Agents (administration & dosage)
• Benzothiazoles (administration & dosage)
• Cytoprotection
• Dextrans (administration & dosage)
• Mice
• Myocardial Reperfusion Injury (diagnostic imaging, drug therapy, pathology)
• Nanostructures (administration & dosage)
• Nucleic Acids (metabolism)
• Optical Imaging
• Quinolines (administration & dosage)
• Theranostic Nanomedicine (methods)
• Treatment Outcome