N-Heterocyclic Carbene-Polyethylenimine Platinum Complexes with Potent in Vitro and in Vivo Antitumor Efficacy.
Fiche publication
Date publication
août 2016
Journal
Bioconjugate chemistry
Auteurs
Membres identifiés du Cancéropôle Est :
Dr BELLEMIN-LAPONNAZ Stéphane, Pr FOURNEL Sylvie, Dr FRISCH Benoit
Tous les auteurs :
Chekkat N, Dahm G, Chardon E, Wantz M, Sitz J, Decossas M, Lambert O, Frisch B, Rubbiani R, Gasser G, Guichard G, Fournel S, Bellemin-Laponnaz S
Lien Pubmed
Résumé
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.
Référence
Bioconjug. Chem.. 2016 Aug;27(8):1942-8