title: Interactions of Nitroxide-Conjugated and Non-Conjugated Glycodendrimers with Normal and Cancer Cells and Biocompatibility Studies.
abstract: Poly(propyleneimine) glycodendrimers fully modified with maltose units were administered to different cancer cell lines and their effect on cell viability was evaluated by using MTS assay and flow cytometry. The mechanism of dendrimer-cell interactions was investigated by the electron paramagnetic resonance (EPR) technique by using a new nitroxide-conjugated glycodendrimer. The nitroxide groups did not modify both the biological properties (cell viability and apoptosis degree) of the dendrimers in the presence of the cells and the dendrimer-cell interactions. Since this class of dendrimers is already known to be biocompatible for human healthy cells, noncancer cells such as human peripheral blood mononuclear cells (PBMCs) and macrophages were also treated with the glycodendrimer, and EPR spectra of the nitroxide-conjugated glycodendrimer were compared for cancer and noncancer cells. It was found that this dendrimer selectively affects the cell viability of tumor cells, while, surprisingly, PBMC proliferation is induced. Moreover, H-bond-active glycodendrimer-cell interactions were different for the different cancer cell lines and noncancer cells. The nitroxide-conjugated glycodendrimer was able to interact with the cell membrane and eventually cross it, getting in contact with cytosol antioxidants. This study helps to clarify the potential anticancer effect of this class of dendrimers opening to future applications of these macromolecules as new antitumor agents.
authors.affiliation: Department of Biomolecular Sciences, University of Urbino Carlo Bo , Via Saffi 2, 61029 Urbino, Italy.
authors.forename: Elisa
authors.initials: E
authors.lastname: Andreozzi
authors.affiliation: Department of Biomolecular Sciences, University of Urbino Carlo Bo , Via Saffi 2, 61029 Urbino, Italy.
authors.forename: Antonella
authors.initials: A
authors.lastname: Antonelli
authors.affiliation: Department of Pure and Applied Sciences, University of Urbino Carlo Bo , Via Ca' Le Suore 2/4, 61029 Urbino, Italy.
authors.forename: Michela
authors.initials: M
authors.lastname: Cangiotti
authors.affiliation: Department of Biomolecular Sciences, University of Urbino Carlo Bo , Via Saffi 2, 61029 Urbino, Italy.
authors.forename: Barbara
authors.initials: B
authors.lastname: Canonico
authors.affiliation: Department of Biomolecular Sciences, University of Urbino Carlo Bo , Via Saffi 2, 61029 Urbino, Italy.
authors.forename: Carla
authors.initials: C
authors.lastname: Sfara
authors.affiliation: Department of Biomolecular Sciences, University of Urbino Carlo Bo , Via Saffi 2, 61029 Urbino, Italy.
authors.forename: Anna
authors.initials: A
authors.lastname: Pianetti
authors.affiliation: Department of Biomolecular Sciences, University of Urbino Carlo Bo , Via Saffi 2, 61029 Urbino, Italy.
authors.forename: Francesca
authors.initials: F
authors.lastname: Bruscolini
authors.affiliation: Leibniz Institute of Polymer Research Dresden , Department Bioactive and Responsive Polymers, Hohe Strasse 6, 01069 Dresden, Germany.
authors.forename: Karin
authors.initials: K
authors.lastname: Sahre
authors.affiliation: Leibniz Institute of Polymer Research Dresden , Department Bioactive and Responsive Polymers, Hohe Strasse 6, 01069 Dresden, Germany.
authors.forename: Dietmar
authors.identifier: 0000-0003-4611-8963
authors.initials: D
authors.lastname: Appelhans
authors.affiliation: Department of Biomolecular Sciences, University of Urbino Carlo Bo , Via Saffi 2, 61029 Urbino, Italy.
authors.forename: Stefano
authors.initials: S
authors.lastname: Papa
authors.affiliation: Department of Pure and Applied Sciences, University of Urbino Carlo Bo , Via Ca' Le Suore 2/4, 61029 Urbino, Italy.
authors.forename: Maria Francesca
authors.identifier: 0000-0002-4681-4718
authors.initials: MF
authors.lastname: Ottaviani
mesh_terms: D000970:Antineoplastic Agents / Q000737:chemistry / Q000494:pharmacology*; D045744:Cell Line, Tumor; D049109:Cell Proliferation / Q000187:drug effects; D002470:Cell Survival / Q000187:drug effects*; D050091:Dendrimers / Q000737:chemistry / Q000494:pharmacology*; D004578:Electron Spin Resonance Spectroscopy; D006801:Humans; D007963:Leukocytes, Mononuclear / Q000166:cytology / Q000187:drug effects; D008320:Maltose / Q000031:analogs & derivatives / Q000494:pharmacology; D009369:Neoplasms / Q000188:drug therapy; D009589:Nitrogen Oxides / Q000737:chemistry / Q000494:pharmacology*; D011126:Polypropylenes / Q000737:chemistry / Q000494:pharmacology*
chemical_list: D000970:Antineoplastic Agents; D050091:Dendrimers; D009589:Nitrogen Oxides; D011126:Polypropylenes; C443641:poly(propyleneimine); D008320:Maltose; C039900:nitroxyl