Dual Gene Delivery Reagents From Antiproliferative Alkylphospholipids for Combined Antitumor Therapy.
Fiche publication
Date publication
janvier 2020
Journal
Frontiers in chemistry
Auteurs
Membres identifiés du Cancéropôle Est :
Dr LEBEAU Luc, Dr REMY Jean-Serge, Pr PONS Françoise
Tous les auteurs :
Gaillard B, Remy JS, Pons F, Lebeau L
Lien Pubmed
Résumé
Alkylphospholipids (APLs) have elicited great interest as antitumor agents due to their unique mode of action on cell membranes. However, their clinical applications have been limited so far by high hemolytic activity. Recently, cationic prodrugs of erufosine, a most promising APL, have been shown to mediate efficient intracellular gene delivery, while preserving the antiproliferative properties of the parent APL. Here, cationic prodrugs of the two APLs that are currently used in the clinic, miltefosine, and perifosine, are investigated and compared to the erufosine prodrugs. Their synthesis, stability, gene delivery and self-assembly properties, and hemolytic activity are discussed in detail. Finally, the potential of the pro-miltefosine and pro-perifosine compounds and in combined antitumor therapy is demonstrated using pUNO1-hTRAIL, a plasmid DNA encoding TRAIL, a member of the TNF superfamily. With these pro-APL compounds, we provide a proof of concept for a new promising strategy for cancer therapy combining gene therapy and APL-based chemotherapy.
Mots clés
alkylphospholipid, chemotherapy, erufosine, gene therapy, hemolytic toxicity, miltefosine, perifosine, prodrug
Référence
Front Chem. 2020 ;8:581260