Copper deficiency is implicated in a number of neurological and metabolic diseases. Current treatments for addressing copper deficiency rely on non-specific copper supplementation, which often leads to off-target oxidative damage. In this talk, I will discuss a new, generalizable platform for delivering copper in a tissue-specific manner, specifically highlighting our efforts in developing a molecular chaperone that transports copper to the liver, which is the primary metabolic organ. We synthesize a galactose-functionalized ionophore that essentially serves as a copper-containing “Trojan Horse” that targets liver-localized asialoglycoprotein receptors and only releases copper inside the cell, where the reducing intracellular environment acts as a trigger for copper release. We use a combination of bioluminescence imaging and inductively-coupled plasma mass spectrometry to demonstrate the efficacy and selectivity of our approach in cell culture and mice. Finally, we apply this therapeutic strategy to a high fat diet mouse model of non-alcoholic fatty liver disease (NAFLD) and find that such treatment severely reduces liver steatosis, highlighting the potential of using copper supplementation as a therapeutic avenue for addressing NAFLD.

Modular ionophore platform for treating copper deficiency in fatty liver disease

2019 Fall National Meeting

The official archive and repository for all ACS Meetings & Expositions abstracts and select posters or presentations.