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Actin exposure upon tissue injury is a targetable wound site-specific protein marker
Authors:Erik D. Pendleton  Challise J. Sullivan  Henri H. Sasmor  Kristy D. Bruse  Tifanie B. Mayfield  David L. Valente  Rachel E. Abrams  Richard H. Griffey  John Dresios
Affiliation:1. Leidos, Inc., 10260 Campus Point Drive, San Diego, CA 92121, United States;2. Lovelace Respiratory Research Institute, 2425 Ridgecrest Drive SE, Albuquerque, NM 87108, United States
Abstract:BackgroundIdentification of wound-specific markers would represent an important step toward damaged tissue detection and targeted delivery of biologically important materials to injured sites. Such delivery could minimize the amount of therapeutic materials that must be administered and limit potential collateral damage on nearby normal tissues. Yet, biological markers that are specific for injured tissue sites remain elusive.MethodsIn this study, we have developed an immunohistological approach for identification of protein epitopes specifically exposed in wounded tissue sites.ResultsUsing ex-vivo tissue samples in combination with fluorescently-labeled antibodies we show that actin, an intracellular cytoskeletal protein, is specifically exposed upon injury. The targetability of actin in injured sites has been demonstrated in vivo through the specific delivery of anti-actin conjugated particles to the wounded tissue in a lethal rat model of grade IV liver injury.ConclusionsThese results illustrate that identification of injury-specific protein markers and their targetability for specific delivery is feasible.General significanceIdentification of wound-specific targets has important medical applications as it could enable specific delivery of various products, such as expression vectors, therapeutic drugs, hemostatic materials, tissue healing, or scar prevention agents, to internal sites of penetrating or surgical wounds regardless of origin, geometry or location.
Keywords:Injury  Wound  Bleeding  Hemorrhage  Protein marker  Actin
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