title: Nanovectorization of TRAIL with single wall carbon nanotubes enhances tumor cell killing.
abstract: 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. Because 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, nonsmall 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.
authors.affiliation: Laboratoire de Nanomédecine, Imagerie et Thérapeutique, EA 4662, UFR Sciences & Techniques, CHU Jean Minjoz, Université de Franche-Comté , 25030 Besançon cedex, France.
authors.forename: Al Batoul
authors.initials: AB
authors.lastname: Zakaria
authors.forename: Fabien
authors.initials: F
authors.lastname: Picaud
authors.forename: Thibault
authors.initials: T
authors.lastname: Rattier
authors.forename: Marc
authors.initials: M
authors.lastname: Pudlo
authors.forename: Florent
authors.initials: F
authors.lastname: Dufour
authors.forename: Lucien
authors.initials: L
authors.lastname: Saviot
authors.forename: Rémi
authors.initials: R
authors.lastname: Chassagnon
authors.forename: Jeannine
authors.initials: J
authors.lastname: Lherminier
authors.forename: Tijani
authors.initials: T
authors.lastname: Gharbi
authors.forename: Olivier
authors.initials: O
authors.lastname: Micheau
authors.forename: Guillaume
authors.initials: G
authors.lastname: Herlem
mesh_terms: D045744:Cell Line, Tumor; D006801:Humans; D046529:Microscopy, Electron, Transmission; D037742:Nanotubes, Carbon / Q000737:chemistry; D009369:Neoplasms / Q000473:pathology*; D053220:Receptors, TNF-Related Apoptosis-Inducing Ligand / Q000378:metabolism; D053221:TNF-Related Apoptosis-Inducing Ligand / Q000737:chemistry* / Q000378:metabolism
chemical_list: D037742:Nanotubes, Carbon; D053220:Receptors, TNF-Related Apoptosis-Inducing Ligand; D053221:TNF-Related Apoptosis-Inducing Ligand; C505653:TNFSF10 protein, human
keywords: Carbon nanotubes; TRAIL; cancer therapy; death receptor; nanomedicine; nanovector