Gadolinium-Based Nanoparticles Can Overcome the Radioresistance of Head and Neck Squamous Cell Carcinoma Through the Induction of Autophagy
Stéphanie Simonet, Claire Rodriguez‐Lafrasse, David M. Beal, Sophie Gerbaud, Céline Malésys, Olivier Tillement, François Lux, Hussein Fayyad‐Kazan, W. Rachidi, Dominique Ardail
Abstract
Radiation therapy is a mainstay in the therapeutic management of Head and Neck Squamous Cell Carcinoma (HNSCC). Despite significant progress in this field, radioresistance still accounts for most treatment failures. Gadolinium-based nanoparticles (GBNs) have shown great promises as radiosensitizers but the underlying sensitizing mechanism is still largely unknown with regards to the disparities obtained in in vitro studies. In this study, we show that a new formulation of GBNs, AGuIX ® , can radiosensitize HNSCC after cell uptake and further accumulation in lysosomes. Although radiation alone triggered late apoptosis and mitochondrial impairment, the pre-treatment with GBNs led to complex DNA damage and a specific increase of autophagic cell death. In addition, a significant radio-enhancement effect was obtained after the pre-conditioning of cells with a glutathione inhibitor before GBNs treatment and radiation exposure. Overall, our results provide additional information on the radio-enhancing properties of GBNs in the management of radioresistant HNSCC.