title: d-Fructose-Decorated Poly(ethylene imine) for Human Breast Cancer Cell Targeting.
abstract: The high affinity of GLUT5 transporter for d-fructose in breast cancer cells has been discussed intensely. In this contribution, high molar mass linear poly(ethylene imine) (LPEI) is functionalized with d-fructose moieties to combine the selectivity for the GLUT5 transporter with the delivery potential of PEI for genetic material. The four-step synthesis of a thiol-group bearing d-fructose enables the decoration of a cationic polymer backbone with d-fructose via thiol-ene photoaddition. The functionalization of LPEI is confirmed by 2D NMR techniques, elemental analysis, and size exclusion chromatography. Importantly, a d-fructose decoration of 16% renders the polymers water-soluble and eliminates the cytotoxicity of PEI in noncancer L929 cells, accompanied by a reduced unspecific cellular uptake of the genetic material. In contrast, the cytotoxicity as well as the cell specific uptake is increased for triple negative MDA-MB-231 breast cancer cells. Therefore, the introduction of d-fructose shows superior potential for cell targeting, which can be assumed to be GLUT5 dependent.
authors.affiliation: Laboratory of Organic and Macromolecular Chemistry (IOMC), Friedrich Schiller University Jena, Humboldtstrasse 10, 07743, Jena, Germany.|Jena Center for Soft Matter (JCSM), Friedrich Schiller University Jena, Philosophenweg 7, 07743, Jena, Germany.
authors.forename: Christoph
authors.initials: C
authors.lastname: Englert
authors.affiliation: Laboratory of Organic and Macromolecular Chemistry (IOMC), Friedrich Schiller University Jena, Humboldtstrasse 10, 07743, Jena, Germany.|Jena Center for Soft Matter (JCSM), Friedrich Schiller University Jena, Philosophenweg 7, 07743, Jena, Germany.
authors.forename: Michael
authors.initials: M
authors.lastname: Pröhl
authors.affiliation: Laboratory of Organic and Macromolecular Chemistry (IOMC), Friedrich Schiller University Jena, Humboldtstrasse 10, 07743, Jena, Germany.|Jena Center for Soft Matter (JCSM), Friedrich Schiller University Jena, Philosophenweg 7, 07743, Jena, Germany.
authors.forename: Justyna A
authors.initials: JA
authors.lastname: Czaplewska
authors.affiliation: Laboratory of Organic and Macromolecular Chemistry (IOMC), Friedrich Schiller University Jena, Humboldtstrasse 10, 07743, Jena, Germany.|Jena Center for Soft Matter (JCSM), Friedrich Schiller University Jena, Philosophenweg 7, 07743, Jena, Germany.
authors.forename: Carolin
authors.initials: C
authors.lastname: Fritzsche
authors.affiliation: Laboratory of Organic and Macromolecular Chemistry (IOMC), Friedrich Schiller University Jena, Humboldtstrasse 10, 07743, Jena, Germany.|Jena Center for Soft Matter (JCSM), Friedrich Schiller University Jena, Philosophenweg 7, 07743, Jena, Germany.
authors.forename: Elisabeth
authors.initials: E
authors.lastname: Preußger
authors.affiliation: Laboratory of Organic and Macromolecular Chemistry (IOMC), Friedrich Schiller University Jena, Humboldtstrasse 10, 07743, Jena, Germany.|Jena Center for Soft Matter (JCSM), Friedrich Schiller University Jena, Philosophenweg 7, 07743, Jena, Germany.
authors.forename: Ulrich S
authors.initials: US
authors.lastname: Schubert
authors.affiliation: Laboratory of Organic and Macromolecular Chemistry (IOMC), Friedrich Schiller University Jena, Humboldtstrasse 10, 07743, Jena, Germany.|Jena Center for Soft Matter (JCSM), Friedrich Schiller University Jena, Philosophenweg 7, 07743, Jena, Germany.
authors.forename: Anja
authors.initials: A
authors.lastname: Traeger
authors.affiliation: Laboratory of Organic and Macromolecular Chemistry (IOMC), Friedrich Schiller University Jena, Humboldtstrasse 10, 07743, Jena, Germany.|Jena Center for Soft Matter (JCSM), Friedrich Schiller University Jena, Philosophenweg 7, 07743, Jena, Germany.
authors.forename: Michael
authors.initials: M
authors.lastname: Gottschaldt
mesh_terms: D001943:Breast Neoplasms / Q000235:genetics / Q000378:metabolism / Q000473:pathology / Q000628:therapy; D045744:Cell Line, Tumor; D005260:Female; D005632:Fructose / Q000737:chemistry / Q000494:pharmacology; D018014:Gene Transfer Techniques; D061307:Human Umbilical Vein Endothelial Cells; D006801:Humans; D011094:Polyethyleneimine / Q000737:chemistry / Q000494:pharmacology
chemical_list: D005632:Fructose; D011094:Polyethyleneimine
keywords: cell-type specific uptake; d-fructose, poly(ethylene imine); nonviral gene delivery; triple-negative MDA-MB-231 breast cancer