Center for Sepsis Control and Care and Department of Anesthesiology and Intensive Care Medicine, Jena University Hospital
Prof. Dr. Britta Qualmann
Institute of Biochemistry I, Jena University Hospital
The liver plays a pivotal role in the host response to life-threatening infections. Its capacity to excrete toxic substances via the bile appears exceptionally sensitive to inflammation, a hallmark of life-threatening infections. From a molecular point of view, the failure to produce bile can be explained by down-regulation of transport proteins at the plasma membrane of liver cells facing the bile canaliculi. In our previous work we have shown that failure to produce bile and excrete toxic compounds from the liver is a common problem, portends poor outcome and depends on pluripotent signaling molecules. Thus, mice lacking these signaling molecules are protected against such negative effects.
However, these molecules also play a crucial role in the recruitment of immune cells to the focus of infection and in their ability to kill bacteria. As unselective suppression of such effector molecules and the concomitant severe immune defect outweigh the beneficial effect on liver function. NanoDyeLivery attempts to unravel the mechanisms of signal molecule-dependent dysfunctions of the bile-producing machinery and to specifically modulate such molecules in the liver while preventing off-target effects on the immune system.
Nanoparticles have been proven to offer unique properties to overcome cellular barriers in order to improve delivery of drugs. We have observed that the fluorescent dye DY635 selectively enters liver cells and used this finding to design hepatocyte-specific nanoparticles. As immune cells do not take up the drug-loaded particles, we will address whether the modulation of intracellular signaling molecules prevents the failure to produce bile without a concomitant impairment of the immune system and thereby enable a novel treatment option.