Grafting TRAIL through Either Amino or Carboxylic Groups onto Maghemite Nanoparticles: Influence on Pro-Apoptotic Efficiency
Hanene Belkahla,
Andrei Alexandru Constantinescu,
Tijani Gharbi,
Florent Barbault,
Alexandre Chevillot-Biraud,
Philippe Decorse,
Olivier Micheau,
Miryana Hémadi,
Souad Ammar
Affiliations
Hanene Belkahla
Université de Paris, CNRS-UMR 7086, Interfaces, Traitements, Organisation et DYnamique des Systèmes (ITODYS), UFR de Chimie, 15 rue Jean-Antoine de Baïf, 75013 Paris, France
Andrei Alexandru Constantinescu
Lipides Nutrition Cancer, INSERM-UMR 1231, Université de Bourgogne Franche-Comté, UFR Science de Santé, 7 Bd Jeanne d’Arc, 21000 Dijon, France
Tijani Gharbi
Nanomedicine, Imagery and Therapeutics, EA 4662, Université de Bourgogne Franche-Comté, UFR Sciences & Techniques, 16 Route de Gray, 25030 Besançon CEDEX, France
Florent Barbault
Université de Paris, CNRS-UMR 7086, Interfaces, Traitements, Organisation et DYnamique des Systèmes (ITODYS), UFR de Chimie, 15 rue Jean-Antoine de Baïf, 75013 Paris, France
Alexandre Chevillot-Biraud
Université de Paris, CNRS-UMR 7086, Interfaces, Traitements, Organisation et DYnamique des Systèmes (ITODYS), UFR de Chimie, 15 rue Jean-Antoine de Baïf, 75013 Paris, France
Philippe Decorse
Université de Paris, CNRS-UMR 7086, Interfaces, Traitements, Organisation et DYnamique des Systèmes (ITODYS), UFR de Chimie, 15 rue Jean-Antoine de Baïf, 75013 Paris, France
Olivier Micheau
Lipides Nutrition Cancer, INSERM-UMR 1231, Université de Bourgogne Franche-Comté, UFR Science de Santé, 7 Bd Jeanne d’Arc, 21000 Dijon, France
Miryana Hémadi
Université de Paris, CNRS-UMR 7086, Interfaces, Traitements, Organisation et DYnamique des Systèmes (ITODYS), UFR de Chimie, 15 rue Jean-Antoine de Baïf, 75013 Paris, France
Souad Ammar
Université de Paris, CNRS-UMR 7086, Interfaces, Traitements, Organisation et DYnamique des Systèmes (ITODYS), UFR de Chimie, 15 rue Jean-Antoine de Baïf, 75013 Paris, France
Tumor necrosis factor (TNF)-related apoptosis-inducing ligand (TRAIL) is a member of the TNF cytokine superfamily. TRAIL is able to induce apoptosis through engagement of its death receptors DR4 and DR5 in a wide variety of tumor cells while sparing vital normal cells. This makes it a promising agent for cancer therapy. Here, we present two different ways of covalently grafting TRAIL onto maghemite nanoparticles (NPs): (a) by using carboxylic acid groups of the protein to graft it onto maghemite NPs previously functionalized with amino groups, and (b) by using the amino functions of the protein to graft it onto NPs functionalized with carboxylic acid groups. The two resulting nanovectors, NH-TRAIL@NPs-CO and CO-TRAIL@NPs-NH, were thoroughly characterized. Biological studies performed on human breast and lung carcinoma cells (MDA-MB-231 and H1703 cell lines) established these nanovectors are potential agents for cancer therapy. The pro-apoptotic effect is somewhat greater for CO-TRAIL@NPs-NH than NH-TRAIL@NPs-CO, as evidenced by viability studies and apoptosis analysis. A computational study indicated that regardless of whether TRAIL is attached to NPs through an acid or an amino group, DR4 recognition is not affected in either case.