Pendleton Erik D, Sullivan Challise J, Sasmor Henri H, Bruse Kristy D, Mayfield Tifanie B, Valente David L, Abrams Rachel E, Griffey Richard H, Dresios John
Leidos, Inc., 10260 Campus Point Drive, San Diego, CA 92121, United States.
Lovelace Respiratory Research Institute, 2425 Ridgecrest Drive SE, Albuquerque, NM 87108, United States.
Biochem Biophys Rep. 2016 May 18;7:56-62. doi: 10.1016/j.bbrep.2016.05.013. eCollection 2016 Sep.
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.
In this study, we have developed an immunohistological approach for identification of protein epitopes specifically exposed in wounded tissue sites.
Using 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 through the specific delivery of anti-actin conjugated particles to the wounded tissue in a lethal rat model of grade IV liver injury.
These results illustrate that identification of injury-specific protein markers and their targetability for specific delivery is feasible.
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.
识别伤口特异性标志物将是朝着检测受损组织以及将具有生物学重要性的物质靶向递送至损伤部位迈出的重要一步。这种递送可以使必须施用的治疗物质的量最小化,并限制对附近正常组织的潜在附带损害。然而,针对受损组织部位的生物标志物仍然难以捉摸。
在本研究中,我们开发了一种免疫组织学方法,用于识别在受伤组织部位特异性暴露的蛋白质表位。
使用组织样本结合荧光标记抗体,我们发现肌动蛋白(一种细胞内细胞骨架蛋白)在损伤时会特异性暴露。在IV级肝损伤致死大鼠模型中,通过将抗肌动蛋白缀合颗粒特异性递送至受伤组织,已证明肌动蛋白在损伤部位具有靶向性。
这些结果表明,识别损伤特异性蛋白质标志物及其特异性递送的靶向性是可行的。
识别伤口特异性靶点具有重要的医学应用,因为它可以使各种产品,如表达载体、治疗药物、止血材料、组织愈合或瘢痕预防剂,能够特异性递送至穿透性或手术伤口的内部部位,而不论其起源、几何形状或位置如何。