Alkoxyamines: Toward a New Family of Theranostic Agents against Cancer - CNRS - Centre national de la recherche scientifique Accéder directement au contenu
Article Dans Une Revue Molecular Pharmaceutics Année : 2014

Alkoxyamines: Toward a New Family of Theranostic Agents against Cancer

Résumé

Theranostics combines therapeutic and diagnostic or drug deposition monitoring abilities of suitable molecules. Here we describe the first steps of building an alkoxyamine-based theranostic agent against cancer. The labile alkoxyamine ALK-1 (t(1/2) = min at 37 degrees C) cleaves spontaneously to generate (1) a highly reactive free alkyl radical used as therapeutic agents to induce cell damages leading to cell death and (2) a stable nitroxide used as contrast agent for Overhauser-enhanced magnetic resonance imaging (OMR). The ALK-1 toxicity was studied extensively in vitro on the glioblastoma cell line U87-MG. Cell viability appeared to be dependent on ALK-1 concentration and on the time of the observation following alkoxyamine treatment. For instance, the LC50 at 72 h was 250 mu M. Data showed that cell toxicity was specifically due to the in situ released alkyl radical. This radical induced oxidative stress, mitochondrial changes, and ultimately the U87 cell apoptosis. The nitroxide production, during the alkoxyamine homolysis, was monitored by OMRI, showing a progressive MRI signal enhancement to 6-fold concomitant to the ALK-1 homolysis. In conclusion, we have demonstrated for the first time that the alkoxyamines are promising molecules to build theranostic tools against solid tumors.

Domaines

Chimie
Fichier non déposé

Dates et versions

hal-01460538 , version 1 (07-02-2017)

Identifiants

Citer

Damien Moncelet, Pierre Voisin, Neha Koonjoo, Véronique Bouchaud, Philippe Massot, et al.. Alkoxyamines: Toward a New Family of Theranostic Agents against Cancer. Molecular Pharmaceutics, 2014, 11 (7), pp.2412--2419. ⟨10.1021/mp5001394⟩. ⟨hal-01460538⟩
43 Consultations
0 Téléchargements

Altmetric

Partager

Gmail Facebook X LinkedIn More