title: Polyglycerol-Based Copper Chelators for the Transport and Release of Copper Ions in Biological Environments.
abstract: 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 first 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 (IC50 > 100 × 10(-6) M (unloaded), 1500 × 10(-6) M Cu(II); Cu:carrier 29:1), and the highest stability in human serum.
authors.affiliation: Institute of Chemistry and Biochemistry, Freie Universität Berlin, Takustr. 3, 14195, Berlin, Germany.
authors.forename: Ralf
authors.initials: R
authors.lastname: Albrecht
authors.affiliation: Institute of Chemistry and Biochemistry, Freie Universität Berlin, Thielallee 63, 14195, Berlin, Germany.
authors.forename: Susanne
authors.initials: S
authors.lastname: Fehse
authors.affiliation: Institute of Radiopharmaceutical Cancer Research, Helmholtz-Zentrum Dresden - Rossendorf (HZDR), Bautzner Landstrasse 400, 01328, Dresden, Germany.
authors.forename: Kritee
authors.initials: K
authors.lastname: Pant
authors.affiliation: Institute of Chemistry and Biochemistry, Freie Universität Berlin, Takustr. 3, 14195, Berlin, Germany.
authors.forename: Sabrina
authors.initials: S
authors.lastname: Nowag
authors.affiliation: Institute of Radiopharmaceutical Cancer Research, Helmholtz-Zentrum Dresden - Rossendorf (HZDR), Bautzner Landstrasse 400, 01328, Dresden, Germany.
authors.forename: Holger
authors.initials: H
authors.lastname: Stephan
authors.affiliation: Institute of Chemistry and Biochemistry, Freie Universität Berlin, Takustr. 3, 14195, Berlin, Germany.
authors.forename: Rainer
authors.initials: R
authors.lastname: Haag
authors.affiliation: Institute of Chemistry and Biochemistry, Freie Universität Berlin, Takustr. 3, 14195, Berlin, Germany.
authors.forename: Carl Christoph
authors.initials: CC
authors.lastname: Tzschucke
mesh_terms: D002614:Chelating Agents / Q000737:chemistry / Q000493:pharmacokinetics; D003300:Copper / Q000737:chemistry / Q000493:pharmacokinetics; D004337:Drug Carriers / Q000737:chemistry / Q000493:pharmacokinetics; D005990:Glycerol / Q000737:chemistry / Q000493:pharmacokinetics; D006801:Humans; D006863:Hydrogen-Ion Concentration; D053758:Nanoparticles / Q000737:chemistry*; D011108:Polymers / Q000737:chemistry / Q000493:pharmacokinetics; D044967:Serum / Q000737:chemistry
chemical_list: D002614:Chelating Agents; D004337:Drug Carriers; D011108:Polymers; C043941:polyglycerol; D003300:Copper; D005990:Glycerol
keywords: Cu ion transport; cellular uptake; nanoparticle; polyglycerol-based; radio labeling