title: N-Heterocyclic Carbene-Polyethylenimine Platinum Complexes with Potent in Vitro and in Vivo Antitumor Efficacy.
abstract: The current interest for platinum N-heterocyclic carbene complexes in cancer research stems from their impressive toxicity reported against a range of different human cancer cells. To date, the demonstration of their in vivo efficacy relative to that of established platinum-based drugs has not been specifically addressed. Here, we introduce an innovative approach to increase the NHC-Pt complex potency whereby multiple NHC-Pt(II) complexes are coordinated along a polyethylenimine polymer (PEI) chain. We show that such NHC-Pt(II)-PEI conjugates induce human cancer cell death in vitro and in vivo in a xenograft mouse model with no observable side effects in contrast to oxaliplatin. Additional studies indicate nucleus and mitochondria targeting and suggest various mechanisms of action compared to classical platinum-based anticancer drugs.
authors.affiliation: Faculté de Pharmacie, Université de Strasbourg-CNRS UMR 7199 , Route du Rhin, BP 60024, 67401 Illkirch cedex, France.
authors.forename: Neila
authors.initials: N
authors.lastname: Chekkat
authors.affiliation: Institut de Physique et Chimie des Matériaux de Strasbourg Université de Strasbourg-CNRS UMR 7504 , 23 rue du Loess, BP 43, 67034 Strasbourg cedex 2, France.
authors.forename: Georges
authors.initials: G
authors.lastname: Dahm
authors.affiliation: Institut de Physique et Chimie des Matériaux de Strasbourg Université de Strasbourg-CNRS UMR 7504 , 23 rue du Loess, BP 43, 67034 Strasbourg cedex 2, France.|Université de Bordeaux, Institut Européen de Chimie et Biologie , 2 rue Robert Escarpit, 33607 Pessac, France.|CNRS, CBMN, UMR 5248 , 33600 Pessac, France.
authors.forename: Edith
authors.initials: E
authors.lastname: Chardon
authors.affiliation: Faculté de Pharmacie, Université de Strasbourg-CNRS UMR 7199 , Route du Rhin, BP 60024, 67401 Illkirch cedex, France.
authors.forename: May
authors.initials: M
authors.lastname: Wantz
authors.affiliation: Faculté de Pharmacie, Université de Strasbourg-CNRS UMR 7199 , Route du Rhin, BP 60024, 67401 Illkirch cedex, France.
authors.forename: Justine
authors.initials: J
authors.lastname: Sitz
authors.affiliation: Université de Bordeaux, Institut Européen de Chimie et Biologie , 2 rue Robert Escarpit, 33607 Pessac, France.|CNRS, CBMN, UMR 5248 , 33600 Pessac, France.
authors.forename: Marion
authors.initials: M
authors.lastname: Decossas
authors.affiliation: Université de Bordeaux, Institut Européen de Chimie et Biologie , 2 rue Robert Escarpit, 33607 Pessac, France.
authors.forename: Olivier
authors.initials: O
authors.lastname: Lambert
authors.affiliation: Faculté de Pharmacie, Université de Strasbourg-CNRS UMR 7199 , Route du Rhin, BP 60024, 67401 Illkirch cedex, France.
authors.forename: Benoit
authors.initials: B
authors.lastname: Frisch
authors.affiliation: Department of Chemistry, University of Zurich , Winterthurerstrasse 190, CH-8057 Zurich, Switzerland.
authors.forename: Riccardo
authors.initials: R
authors.lastname: Rubbiani
authors.affiliation: Department of Chemistry, University of Zurich , Winterthurerstrasse 190, CH-8057 Zurich, Switzerland.
authors.forename: Gilles
authors.initials: G
authors.lastname: Gasser
authors.affiliation: Université de Bordeaux, Institut Européen de Chimie et Biologie , 2 rue Robert Escarpit, 33607 Pessac, France.|CNRS, CBMN, UMR 5248 , 33600 Pessac, France.
authors.forename: Gilles
authors.initials: G
authors.lastname: Guichard
authors.affiliation: Faculté de Pharmacie, Université de Strasbourg-CNRS UMR 7199 , Route du Rhin, BP 60024, 67401 Illkirch cedex, France.
authors.forename: Sylvie
authors.initials: S
authors.lastname: Fournel
authors.affiliation: Institut de Physique et Chimie des Matériaux de Strasbourg Université de Strasbourg-CNRS UMR 7504 , 23 rue du Loess, BP 43, 67034 Strasbourg cedex 2, France.
authors.forename: Stéphane
authors.initials: S
authors.lastname: Bellemin-Laponnaz
mesh_terms: D000818:Animals; D000970:Antineoplastic Agents / Q000737:chemistry* / Q000378:metabolism / Q000494:pharmacology*; D001692:Biological Transport; D045744:Cell Line, Tumor; D006801:Humans; D051379:Mice; D008928:Mitochondria / Q000187:drug effects / Q000378:metabolism; D009944:Organoplatinum Compounds / Q000737:chemistry* / Q000378:metabolism / Q000494:pharmacology*; D011094:Polyethyleneimine / Q000737:chemistry*; D023041:Xenograft Model Antitumor Assays
chemical_list: D000970:Antineoplastic Agents; D009944:Organoplatinum Compounds; C569970:Pt-NHC complex; D011094:Polyethyleneimine