Polyglycerol-Based Copper Chelators for the Transport and Release of Copper Ions in Biological Environments


Polyglycerol-Based Copper Chelators for the Transport and Release of Copper Ions in Biological Environments

Albrecht, R.; Fehse, S.; Pant, K.; Nowag, S.; Stephan, H.; Haag, R.; Tzschucke, C. C.

Here, the synthesis and characterization of three improved nanosystems is presented based on amino functionalized hyperbranched polyglycerol (hPG; M w = 16.8 kDa) as potential copper( II ) chelators. The ligands, N -methyl- N -picolylglycine amide, 2,6-pyridine dicarboxylic acid monoamide, and cyclam tetraacetic acid (TETA) monoamide, are covalently attached to the polymer with amide bonds. In this paper, the Cu( II ) loading capacity, the stability of the Cu( II )- loaded carriers at different pHs, with competing ligands and in human serum, as well as the transport of Cu( II ) in biological systems are investigated. For the fi rst time, a different cytotoxicity of functionalized polymer nanoparticles with and without Cu( II ) is observed. The cyclam-based carrier combines the highest loading capacity (29 Cu ions/nanoparticle), best stability with respect to pH and EDTA (45% remaining Cu after 24 h), lowest cytotoxicity (IC 50 > 100 × 10 −6 M (unloaded), 1500 × 10 −6 M Cu( II ); Cu:carrier 29:1), and the highest stability in human serum.

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Publ.-Id: 23584