报告人：Zhenjia Wang, PhD，Research Assistant Professor

　　             Department of Pharmacology, College of Medicine

　　             Department of Bioengineering, College of Engineering

　　             University of Illinois at Chicago

　　主持人：韩晶岩教授，北京大学基础医学院中西医结合教研室主任

　　             北京大学医学部天士力微循环研究中心主任

　　时间：2012年8月31日15：00--16：30

　　地点：逸夫楼407教室

　　继续教育I类1学分

　　 北京大学基础医学院中西医结合教研室

　　 北京大学医学部天士力微循环研究中心

　　Abstract:

Acute lung injury is a life-threatening disease, mainly due to neutrophil infiltration and dysfunction of bilateral barrier leading to a failure of gas exchange in the lung. Therapy of drug interventions is limited, possibly because of current inability to efficiently deliver anti-inflammatory drugs to the site of pathology in a sustained manner. In my talk, I will first discuss the molecular mechanism which regulates uptake and transport of fluorescently-labeled polymer nanoparticles in pulmonary endothelial cells by the design of biofunctional polymer nanoparticles, single nanoparticle imaging, live cell imaging and genetic mice. We found that albumin-conjugated nanoparticles (size of 20-100nm in diameter) can be internalized by endothelial caveolae and efficiently transport into tissue via caveolar cargo. Based on these results, we postulated that such a mechanism would efficiently deliver therapeutics to treat lung inflammatory injury. To achieve this goal, the second part of my talk is focused on design and characterization of albumin nanoparticles capable of carrying fluorescent probes and therapeutics (a glucocorticoid drug, dexamethasone (Dex)). We evaluated the therapeutic effects of Dex-incorporated albumin nanoparticles in a mouse model of lung injury induced by lipopolysacchride (LPS). The results showed that Dex-albumin nanoparticles were more efficient in protecting against lung inflammatory injury as evidenced by reduction of neutrophil infiltration compared to free Dex alone. Sustainable release of Dex from albumin nanoparticles downregulated endothelial expression of ICAM-1 required for neutrophil infiltration. Our results provide a proof of concept that targeting the lung vasculature with albumin nanoparticles is a useful strategy preventing lung inflammatory injury.