N-Heterocyclic Carbene-Polyethylenimine Platinum Complexes with Potent in Vitro and in Vivo Antitumor Efficacy

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

*Corresponding author for this work

Research output: Contribution to journalArticleResearchpeer-review

33 Citations (Scopus)

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.

Original languageEnglish
Pages (from-to)1942-1948
Number of pages7
JournalBioconjugate Chemistry
Volume27
Issue number8
DOIs
Publication statusPublished - 17 Aug 2016
Externally publishedYes

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