Service interruption on Monday 11 July from 12:30 to 13:00: all the sites of the CCSD (HAL, EpiSciences, SciencesConf, AureHAL) will be inaccessible (network hardware connection).
Skip to Main content Skip to Navigation
Journal articles

TRAIL acts synergistically with iron oxide nanocluster-mediated magneto- and photothermia

Abstract : Targeting TRAIL (Tumor necrosis factor (TNF)-Related Apoptosis-Inducing Ligand) receptors for cancer therapy remains challenging due to tumor cell resistance and poor preparations of TRAIL or its derivatives. Herein, to optimize its therapeutic use, TRAIL was grafted onto iron oxide nanoclusters (NCs) with the aim of increasing its pro-apoptotic potential through nanoparticle-mediated magnetic hyperthermia (MHT) or photothermia (PT). Methods: The nanovector, NC@TRAIL, was characterized in terms of size, grafting efficiency, and potential for MHT and PT. The therapeutic function was assessed on a TRAIL-resistant breast cancer cell line, MDA-MB-231, wild type (WT) or TRAIL-receptor-deficient (DKO), by combining complementary methylene blue assay and flow cytometry detection of apoptosis and necrosis. Results: Combined with MHT or PT under conditions of "moderate hyperthermia" at low concentrations, NC@TRAIL acts synergistically with the TRAIL receptor to increase the cell death rate beyond what can be explained by the mere global elevation of temperature. In contrast, all results are consistent with the idea that there are hotspots, close to the nanovector and, therefore, to the membrane receptor, which cause disruption of the cell membrane. Furthermore, nanovectors targeting other membrane receptors, unrelated to the TNF superfamily, were also found to cause tumor cell damage upon PT. Indeed, functionalization of NCs by transferrin (NC@Tf) or human serum albumin (NC@HSA) induces tumor cell killing when combined with PT, albeit less efficiently than NC@TRAIL. Conclusions: Given that magnetic nanoparticles can easily be functionalized with molecules or proteins recognizing membrane receptors, these results should pave the way to original remote-controlled antitumoral targeted thermal therapies.
Document type :
Journal articles
Complete list of metadata
Contributor : Olivier Micheau Connect in order to contact the contributor
Submitted on : Friday, January 7, 2022 - 1:15:37 PM
Last modification on : Sunday, June 26, 2022 - 1:57:58 AM
Long-term archiving on: : Friday, April 8, 2022 - 7:15:24 PM


Publication funded by an institution



Hanene Belkahla, Eva Mazarío, Anouchka Plan Sangnier, John Lomas, Tijani Gharbi, et al.. TRAIL acts synergistically with iron oxide nanocluster-mediated magneto- and photothermia. Theranostics, Ivyspring International Publisher, 2019, 9 (20), pp.5924-5936. ⟨10.7150/thno.36320⟩. ⟨inserm-03516746⟩



Record views


Files downloads