TY - JOUR
T1 - N-Heterocyclic Carbene-Polyethylenimine Platinum Complexes with Potent in Vitro and in Vivo Antitumor Efficacy
AU - Chekkat, Neila
AU - Dahm, Georges
AU - Chardon, Edith
AU - Wantz, May
AU - Sitz, Justine
AU - Decossas, Marion
AU - Lambert, Olivier
AU - Frisch, Benoit
AU - Rubbiani, Riccardo
AU - Gasser, Gilles
AU - Guichard, Gilles
AU - Fournel, Sylvie
AU - Bellemin-Laponnaz, Stéphane
N1 - Funding Information:
The authors gratefully acknowledge the CNRS, the MESR for a PhD grant to N.C., G.D., and E.C, the Swiss National Science Foundation (Professorships Nos. PP00P2-133568 and PP00P2-157545 to G. Ga), the University of Zurich (G. Ga), the Stiftung fur Wissenschaftliche Forschung of the University of Zurich (G. Ga), the Novartis Jubilee Foundation (G.Ga and R.R), the Forschungskredit of the University of Zurich (R.R.), and the UBS Promedica Stiftung (G.Ga and R.R.). In addition, this work has been founded by the Initiative of Excellence (IdEx), University of Strasbourg, and by La Ligue contre le Cancer - Region Grand Est. The authors are very grateful to the Department of Veterinary Biochemistry and the Molecular Biology of the University of Zurich for access to state-of-the-art technology.
Publisher Copyright:
© 2016 American Chemical Society.
PY - 2016/8/17
Y1 - 2016/8/17
N2 - 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.
AB - 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.
UR - http://www.scopus.com/inward/record.url?scp=84983516184&partnerID=8YFLogxK
U2 - 10.1021/acs.bioconjchem.6b00320
DO - 10.1021/acs.bioconjchem.6b00320
M3 - Article
C2 - 27459208
AN - SCOPUS:84983516184
SN - 1043-1802
VL - 27
SP - 1942
EP - 1948
JO - Bioconjugate Chemistry
JF - Bioconjugate Chemistry
IS - 8
ER -