Dendritic Nanocarriers for the Selective and Targeted Metal Ion Transport over Biological Barriers

点击翻译按钮获取中文摘要

Copper (Cu) is an important biological cofactor for a number of metalloenzymes and plays a key role in many neurodegenerative diseases, e.g., Alzheimer’s disease and Wilson’s disease. Particularly in case of Alzheimer’s diseases, exogenous supply of Cu to brain is one of the therapeutic approaches for addressing such deficiency symptoms. However, Cu needs to be transported into the central nervous system (CNS) and bypass the blood-brain-barrier (BBB), which remains an unsolved problem. Promising systems for this purpose are nanocarriers, which can bind Cu-ions selectively and release them specifically into the cellular environment in response to biochemical triggers, such as altered pH or ionic strength that is existing in the pathological tissues. In this collaborative project, core-single shell (CS) or core-multishell (CMS) nanocarriers will be designed with a hyperbranched polyglycerol (hPG) core. In order to bind Cu(II) selectively, different copper binding amino ligands will be attached as a shell. Poly(ethylene glycol)-chains will be linked either to the core or to the shell system to generate CS and CMS architectures respectively. These new nanotransporters will then be investigated for their structural organization, self-assembling behavior and metal binding capacity. Substantial physico-chemical investigation will be carried out to explore the mechanism of Cu-entrapment and release. Finally, biochemical tests will be performed to elucidate cellular toxicity, uptake and compartmentalization.