Pro-organic radical contrast agents ("pro-ORCAs") for real-time MRI of pro-drug activation in biological systems.
Fiche publication
Date publication
août 2020
Journal
Polymer chemistry
Auteurs
Membres identifiés du Cancéropôle Est :
Dr DETAPPE Alexandre
Tous les auteurs :
Nguyen HV, Detappe A, Harvey P, Gallagher N, Mathieu C, Agius MP, Zavidij O, Wang W, Jiang Y, Rajca A, Jasanoff A, Ghobrial IM, Ghoroghchian PP, Johnson JA
Lien Pubmed
Résumé
Nitroxide-based organic-radical contrast agents (ORCAs) are promising as safe, next-generation magnetic resonance imaging (MRI) tools. Nevertheless, stimuli-responsive ORCAs that enable MRI monitoring of prodrug activation have not been reported; such systems could open new avenues for prodrug validation and image-guided drug delivery. Here, we introduce a novel "pro-ORCA" concept that addresses this challenge. By covalent conjugation of nitroxides and drug molecules (doxorubicin, DOX) to the same brush-arm star polymer (BASP) through chemically identical cleavable linkers, we demonstrate that pro-ORCA and prodrug activation, , ORCA and DOX release, leads to significant changes in MRI contrast that correlate with cytotoxicity. This approach is shown to be general for a range of commonly used linker cleavage mechanisms (, photolysis and hydrolysis) and release rates. Pro-ORCAs could find applications as research tools or clinically viable "reporter theranostics" for and MRI-correlated prodrug activation.
Référence
Polym Chem. 2020 Aug 7;11(29):4768-4779