title: Nebulized gadolinium-based nanoparticles: a theranostic approach for lung tumor imaging and radiosensitization.
abstract: Lung cancer is the most common and most fatal cancer worldwide. Thus, improving early diagnosis and therapy is necessary. Previously, gadolinium-based ultra-small rigid platforms (USRPs) were developed to serve as multimodal imaging probes and as radiosensitizing agents. In addition, it was demonstrated that USRPs can be detected in the lungs using ultrashort echo-time magnetic resonance imaging (UTE-MRI) and fluorescence imaging after intrapulmonary administration in healthy animals. The goal of the present study is to evaluate their theranostic properties in mice with bioluminescent orthotopic lung cancer, after intrapulmonary nebulization or conventional intravenous administration. It is found that lung tumors can be detected non-invasively using fluorescence tomography or UTE-MRI after nebulization of USRPs, and this is confirmed by histological analysis of the lung sections. The deposition of USRPs around the tumor nodules is sufficient to generate a radiosensitizing effect when the mice are subjected to a single dose of 10 Gy conventional radiation one day after inhalation (mean survival time of 112 days versus 77 days for irradiated mice without USRPs treatment). No apparent systemic toxicity or induction of inflammation is observed. These results demonstrate the theranostic properties of USRPs for the multimodal detection of lung tumors and improved radiotherapy after nebulization.
authors.affiliation: INSERM U823, Institut Albert Bonniot, 38706, Grenoble cedex, France; Université Joseph Fourier, Institut Albert Bonniot, 38706, Grenoble cedex, France; Nano-H S.A.S, 2 place de l'Europe, 38070, Saint Quentin - Fallavier, France.
authors.forename: Sandrine
authors.initials: S
authors.lastname: Dufort
authors.forename: Andrea
authors.initials: A
authors.lastname: Bianchi
authors.forename: Maxime
authors.initials: M
authors.lastname: Henry
authors.forename: François
authors.initials: F
authors.lastname: Lux
authors.forename: Géraldine
authors.initials: G
authors.lastname: Le Duc
authors.forename: Véronique
authors.initials: V
authors.lastname: Josserand
authors.forename: Cédric
authors.initials: C
authors.lastname: Louis
authors.forename: Pascal
authors.initials: P
authors.lastname: Perriat
authors.forename: Yannick
authors.initials: Y
authors.lastname: Crémillieux
authors.forename: Olivier
authors.initials: O
authors.lastname: Tillement
authors.forename: Jean-Luc
authors.initials: JL
authors.lastname: Coll
mesh_terms: D000818:Animals; D002289:Carcinoma, Non-Small-Cell Lung / Q000473:pathology / Q000628:therapy*; D005682:Gadolinium; D006801:Humans; D008175:Lung Neoplasms / Q000473:pathology / Q000628:therapy*; D053768:Metal Nanoparticles; D051379:Mice; D009330:Nebulizers and Vaporizers
chemical_list: D005682:Gadolinium
keywords: intrapulmonary administration; lung cancer; multimodal imaging; radiosensitization; theranostics