Targeting of Drugs to ICAM for Treatment of Acute Lung Injury. Revision
Abstract
In the final fifth year, we finalized research projected for all five Specific Aims of the grant. In the Aim 1, we have analyzed the role of geometry of anti-CAM conjugates in their targeting to endothelial cells. In the Aim 2, we have characterized the roles of mode of GOX targeting, oxygen supply and biological factors controlling acute lung injury in the new mouse model developed in this grant. In the Aim 3, we characterized protective effects of targeting antioxidant enzymes in animal model of oxidative stress caused primarily by H2O2 vs superoxide anion and found that targeting of catalase vs SOD provides effective protection in these cases, respectively. In the Aim 4, we completed characterization of thrombin-activated mutant fusion protein, scFv/uPA-T synthesized in the year 4. In the Aim 5, we have studied protective effects of anti-CAM/AOE and scFv/uPA-T in a mouse model of in situ lung ischemia/reperfusion, established in our group and found that targeting of both antioxidants into endothelium and pro-urokinase to endothelial surface protect the lung against oxidative and thrombotic stress in this clinically relevant model. Taken together, the data accumulated in the course of this grant and analyzed in the final report indicate that targeting of antioxidant and anti-thrombotic enzymes to endothelial CAMs affords significant advantages in treatment of pulmonary oxidative stress and thrombosisintertwinedhallmarksofALI/ARDS.
Document Details
- Document Type
- Technical Report
- Publication Date
- Sep 25, 2007
- Accession Number
- ADA473877
Entities
People
- Vladimir Muzykantov
Organizations
- University of Pennsylvania