دانلود رایگان مقاله نشانگر پروتئینی قابل هدف یابی محل خاص زخم با قرارگیری اکتین

Abstract

Background: Identification 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. Methods: In this study, we have developed an immunohistological approach for identification of protein epitopes specifically exposed in wounded tissue sites. Results: Using 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. Conclusions: These results illustrate that identification of injury-specific protein markers and their targetability for specific delivery is feasible. General significance: Identification 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.

4. Discussion

In this study we describe an approach for identification of injury-specific protein markers that are rapidly exposed in wounded tissues and can be targeted for localized delivery of compounds of interest specifically at the affected area immediately upon trauma. Using this approach we discovered actin as such injury-specific marker. Wound-specific exposure of actin was verified in various animal tissues, suggesting the targetability of this protein independently of tissue type. We further showed that this marker is exposed in trauma areas within seconds upon tissue damage and remains stable over time and in the presence of blood. Importantly, by exploiting this protein as a wound-specific target, we selectively delivered microparticles conjugated to actin antibodies to injured areas in an ex vivo model of animal tissue trauma and an in vivo model of lethal animal injury. Given that tissue injury results in cell lysis and exposure of intracellular components normally not present on the cell surface, it is anticipated that the method described here for discovery of wound-specific epitopes, and the identification of actin as such marker, will be broadly applicable regardless of wound size and/or location.