Nanovectorization of TRAIL with single wall carbon nanotubes enhances tumor cell killing.

Fiche publication


Date publication

janvier 2015

Auteurs

Membres identifiés du Cancéropôle Est :
Dr MICHEAU Olivier, Dr PICAUD Fabien


Tous les auteurs :
Zakaria AB, Picaud F, Rattier T, Pudlo M, Saviot L, Chassagnon R, Lherminier J, Gharbi T, Micheau O, Herlem G

Résumé

Tumor necrosis factor-related apoptosis-inducing ligand (TRAIL or Apo2L) is a member of the tumor necrosis factor (TNF) superfamily. This type II transmembrane protein is able to bound specifically to cancer cell receptors (i.e. TRAIL-R1 (or DR4) and TRAIL-R2 (or DR5)) and to induce apoptosis without being toxic for healthy cells. Since membrane-bound TRAIL induces stronger receptor aggregation and apoptosis than soluble TRAIL, we proposed here to vectorize TRAIL using single walled carbon nanotubes (SWCNTs) to mimic membrane TRAIL. Owing to their exceptional and revolutional properties, carbon nanotubes, especially SWCNTs, are used in a wide range of physical or, now, medical applications. Indeed due to their high mechanical resistance, their high flexibility and their hydrophobicity, SWCNTs are known to rapidly diffuse in an aqueous medium such as blood, opening the way of development of new drug nanovectors (or nanocarriers). Our TRAIL-based SWCNTs nanovectors proved to be more efficient than TRAIL alone death receptors in triggering cancer cell killing. These NPTs increased TRAIL pro-apoptotic potential by nearly 20 fold in different Human tumor cell lines including colorectal, non-small cell lung cancer or hepatocarcinomas. We provide thus a proof-of-concept that TRAIL nanovector derivatives based on SWCNT may be useful to future nanomedicine therapies.

Référence

Nano Lett. 2015 Jan 13.