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

Autor: Gilles Guichard, Stéphane Bellemin-Laponnaz, Marion Decossas, Olivier Lambert, Sylvie Fournel, Riccardo Rubbiani, Georges Dahm, Edith Chardon, Benoît Frisch, Gilles Gasser, May Wantz, Justine Sitz, Neila Chekkat
Přispěvatelé: Institut de Physique et Chimie des Matériaux de Strasbourg (IPCMS), Université de Strasbourg (UNISTRA)-Centre National de la Recherche Scientifique (CNRS)-Matériaux et nanosciences d'Alsace (FMNGE), Institut de Chimie du CNRS (INC)-Université de Strasbourg (UNISTRA)-Université de Haute-Alsace (UHA) Mulhouse - Colmar (Université de Haute-Alsace (UHA))-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-Institut de Chimie du CNRS (INC)-Université de Strasbourg (UNISTRA)-Université de Haute-Alsace (UHA) Mulhouse - Colmar (Université de Haute-Alsace (UHA))-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-Réseau nanophotonique et optique, Centre National de la Recherche Scientifique (CNRS)-Université de Strasbourg (UNISTRA)-Université de Haute-Alsace (UHA) Mulhouse - Colmar (Université de Haute-Alsace (UHA))-Centre National de la Recherche Scientifique (CNRS)-Université de Strasbourg (UNISTRA), Immunologie et chimie thérapeutiques (ICT), Cancéropôle du Grand Est-Centre National de la Recherche Scientifique (CNRS), Ecole Nationale Vétérinaire Agroalimentaire et de l'Alimentation Nantes Atlantique (ONIRIS), Conception et application de molécules bioactives (CAMB), Institut de Chimie du CNRS (INC)-Université de Strasbourg (UNISTRA)-Centre National de la Recherche Scientifique (CNRS), Ecole Nationale Supérieure de Chimie de Paris - Chimie ParisTech-PSL (ENSCP), Université Paris sciences et lettres (PSL), Université Louis Pasteur - Laboratoire Decomet (UMR 7177-LC3), Université Louis Pasteur - Strasbourg I-Commencez à saisir le nom d'une tutelle, University of Zurich, Fournel, Sylvie
Jazyk: angličtina
Rok vydání: 2016
Předmět:
10120 Department of Chemistry
Programmed cell death
Organoplatinum Compounds
Biomedical Engineering
3003 Pharmaceutical Science
Pharmaceutical Science
chemistry.chemical_element
2204 Biomedical Engineering
Bioengineering
Antineoplastic Agents
[SDV.CAN]Life Sciences [q-bio]/Cancer
[CHIM.THER]Chemical Sciences/Medicinal Chemistry
Pharmacology
Mitochondrion
010402 general chemistry
01 natural sciences
chemistry.chemical_compound
Mice
In vivo
Cell Line
Tumor
540 Chemistry
medicine
Animals
Humans
Polyethyleneimine
ComputingMilieux_MISCELLANEOUS
Polyethylenimine
1502 Bioengineering
010405 organic chemistry
Chemistry
Organic Chemistry
Biological Transport
Xenograft Model Antitumor Assays
In vitro
3. Good health
0104 chemical sciences
Oxaliplatin
Mitochondria
3004 Pharmacology
[CHIM.POLY]Chemical Sciences/Polymers
Cancer research
1305 Biotechnology
Platinum
Biotechnology
medicine.drug
Conjugate
1605 Organic Chemistry
Zdroj: Bioconjugate Chemistry
Bioconjugate Chemistry, American Chemical Society, 2016, 27 (8), pp.1942-1948. ⟨10.1021/acs.bioconjchem.6b00320⟩
BASE-Bielefeld Academic Search Engine
ISSN: 1043-1802
1520-4812
DOI: 10.1021/acs.bioconjchem.6b00320⟩
Popis: 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.
Databáze: OpenAIRE
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