1:30 PM - *SB03.02.01
Coupling Pro-Apoptotic TRAIL Factor to Superparamagnetic Iron Oxide Nanoparticles to Build Efficient Nanohybrid Drugs for Cancer Therapy
Souad Ammar1,Hanene Belkahla1,2,Andrei Alexandru Constantinescu2,Tijani Gharbi2,Florent Barbaut1,Miryana Hemadi1
Universite de Paris1,Université Bourgogne Franche-Comté2
Show Abstract
TRAIL (Tumor Necrosis Factor-related apoptosis-inducing ligand), a cytokine belonging to the TNF superfamily, attracted major interest in oncology owing to its selective antitumor properties [1]. Therapeutic clinical trials using soluble TRAIL or antibodies targeting the two main agonist receptors (TRAIL-R1 and TRAIL-R2) have, however, failed to demonstrate their efficacy [2]. Attempts to increase its antitumor activity include, amongst others, its functionalization by nanoparticles [3], particularly magnetic nanoparticles (MNPs). Such carriers allow concentrating TRAIL [4] which can be driven to a defined target site by local application of an external DC-magnetic field. They also offer the possibility of monitoring TRAIL delivery by magnetic resonance imaging (MRI) and the possibility to increase antitumor TRAIL functionality by magnetic hyperthermia [5]. Magnetic iron oxide MNPs, magnetite and maghemite, have the right magnetic properties [6] and exhibit relatively low toxicity [7]. For this reason, they were specifically produced with different average sizes, i.e. 10 and 100 nm (magnetic single core versus magnetic multicore) [4], and were attached to TRAIL through peptide coupling, engaging respectively carboxylic or amino protein group to evaluate both the effect of their size and their chemical bounding on TRAIL antitumoral activity on malignant mammal cells. They were also subsequently submitted to an external AC-magnetic field to confirm their capability to eradicate residual TRAIL resistant tumoral cells through local heating [5]. Clearly, the properties of TRAIL and the multimodal characteristics of MNPs hold great promise for the treatment of cancer and pave the way for the generation of new and efficient drugs.
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