title: Combining ultrasmall gadolinium-based nanoparticles with photon irradiation overcomes radioresistance of head and neck squamous cell carcinoma.
abstract: Gadolinium based nanoparticles (GBNs, diameter 2.9±0.2nm), have promising biodistribution properties for theranostic use in-vivo. We aimed at demonstrating the radiosensitizing effect of these GBNs in experimental radioresistant human head and neck squamous cell carcinoma (SQ20B, FaDu and Cal33 cell lines). Combining 0.6mM GBNs with 250kV photon irradiation significantly decreased SQ20B cell survival, associated with an increase in non-reparable DNA double-strand breaks, the shortening of G2/M phase blockage, and the inhibition of cell proliferation, each contributing to the commitment of late apoptosis. Similarly, radiation resistance was overcome for SQ20B stem-like cells, as well as for FaDu and Cal33 cell lines. Using a SQ20B tumor-bearing mouse model, combination of GBNs with 10Gy irradiation significantly delayed tumor growth with an increase in late apoptosis and a decrease in cell proliferation. These results suggest that GBNs could be envisioned as adjuvant to radiotherapy for HNSCC tumors.
authors.affiliation: Institut Lumière Matière, UMR 5306 CNRS, Université de Lyon, Université Lyon 1, Villeurbanne cedex, France.
authors.forename: Imen
authors.initials: I
authors.lastname: Miladi
authors.affiliation: Laboratoire de Radiobiologie Cellulaire et Moléculaire, EMR3738, Faculté de Médecine Lyon-Sud, Université de Lyon, Université Lyon 1, Oullins, France.
authors.forename: Marie-Thérèse
authors.initials: MT
authors.lastname: Aloy
authors.affiliation: Laboratoire de Radiobiologie Cellulaire et Moléculaire, EMR3738, Faculté de Médecine Lyon-Sud, Université de Lyon, Université Lyon 1, Oullins, France.
authors.forename: Emma
authors.initials: E
authors.lastname: Armandy
authors.affiliation: Institut Lumière Matière, UMR 5306 CNRS, Université de Lyon, Université Lyon 1, Villeurbanne cedex, France.
authors.forename: Pierre
authors.initials: P
authors.lastname: Mowat
authors.affiliation: Institut Lumière Matière, UMR 5306 CNRS, Université de Lyon, Université Lyon 1, Villeurbanne cedex, France; IMTHERNAT, Hôpital Edouard Herriot, Hospices Civils de Lyon, Lyon, France.
authors.forename: David
authors.initials: D
authors.lastname: Kryza
authors.affiliation: Laboratoire de Radiobiologie Cellulaire et Moléculaire, EMR3738, Faculté de Médecine Lyon-Sud, Université de Lyon, Université Lyon 1, Oullins, France.
authors.forename: Nicolas
authors.initials: N
authors.lastname: Magné
authors.affiliation: Institut Lumière Matière, UMR 5306 CNRS, Université de Lyon, Université Lyon 1, Villeurbanne cedex, France.
authors.forename: Olivier
authors.initials: O
authors.lastname: Tillement
authors.affiliation: Institut Lumière Matière, UMR 5306 CNRS, Université de Lyon, Université Lyon 1, Villeurbanne cedex, France.
authors.forename: François
authors.initials: F
authors.lastname: Lux
authors.affiliation: Institut Lumière Matière, UMR 5306 CNRS, Université de Lyon, Université Lyon 1, Villeurbanne cedex, France; IMTHERNAT, Hôpital Edouard Herriot, Hospices Civils de Lyon, Lyon, France.
authors.forename: Claire
authors.initials: C
authors.lastname: Billotey
authors.affiliation: Institut Lumière Matière, UMR 5306 CNRS, Université de Lyon, Université Lyon 1, Villeurbanne cedex, France; IMTHERNAT, Hôpital Edouard Herriot, Hospices Civils de Lyon, Lyon, France.
authors.forename: Marc
authors.initials: M
authors.lastname: Janier
authors.affiliation: Laboratoire de Radiobiologie Cellulaire et Moléculaire, EMR3738, Faculté de Médecine Lyon-Sud, Université de Lyon, Université Lyon 1, Oullins, France; Unité Médicale d'Oncologie Moléculaire et Transfert, Hospices Civils de Lyon, Laboratoire de Biochimie et Biologie Moléculaire, Centre Hospitalier Lyon-Sud, Pierre Bénite, France. Electronic address: claire.rodriguez@univ-lyon1.fr.
authors.forename: Claire
authors.initials: C
authors.lastname: Rodriguez-Lafrasse
mesh_terms: D000818:Animals; D017209:Apoptosis; D002294:Carcinoma, Squamous Cell / Q000188:drug therapy* / Q000473:pathology; D053143:Caspase 2 / Q000378:metabolism; D045744:Cell Line, Tumor; D049109:Cell Proliferation; D002470:Cell Survival; D004249:DNA Damage; D005260:Female; D005434:Flow Cytometry; D005682:Gadolinium / Q000737:chemistry*; D006258:Head and Neck Neoplasms / Q000188:drug therapy* / Q000473:pathology; D006657:Histones / Q000737:chemistry; D006801:Humans; D051379:Mice; D008819:Mice, Nude; D018613:Microscopy, Confocal; D008856:Microscopy, Fluorescence; D050997:Nanomedicine; D053758:Nanoparticles / Q000737:chemistry*; D011838:Radiation-Sensitizing Agents / Q000737:chemistry*; D011878:Radiotherapy
chemical_list: D006657:Histones; D011838:Radiation-Sensitizing Agents; D005682:Gadolinium; D053143:Caspase 2
keywords: Gadolinium nanoparticles; Head and neck squamous cell carcinoma (HNSCC); Radioresistance; Radiosensitization; Radiotherapy