N-Heterocyclic Carbene–Polyethylenimine Platinum Complexes with Potent in Vitro and in Vivo Antitumor Efficacy
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- 作者：Neila Chekkat ; Georges Dahm ; Edith Chardon ; May Wantz ; Justine Sitz ; Marion Decossas ; Olivier Lambert ; Benoit Frisch ; Riccardo Rubbiani ; Gilles Gasser ; Gilles Guichard ; Sylvie Fournel ; Stéphane Bellemin-Laponnaz
- 刊名：Bioconjugate Chemistry
- 出版年：2016
- 出版时间：August 17, 2016
- 年：2016
- 卷：27
- 期：8
- 页码：1942-1948
- 全文大小：520K
- 年卷期：0
- ISSN：1520-4812
文摘
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.