title: Internalization pathways into cancer cells of gadolinium-based radiosensitizing nanoparticles.
abstract: Over the last few decades, nanoparticles have been studied in theranostic field with the objective of exhibiting a long circulation time through the body coupled to major accumulation in tumor tissues, rapid elimination, therapeutic potential and contrast properties. In this context, we developed sub-5 nm gadolinium-based nanoparticles that possess in vitro efficient radiosensitizing effects at moderate concentration when incubated with head and neck squamous cell carcinoma cells (SQ20B). Two main cellular internalization mechanisms were evidenced and quantified: passive diffusion and macropinocytosis. Whereas the amount of particles internalized by passive diffusion is not sufficient to induce in vitro a significant radiosensitizing effect, the cellular uptake by macropinocytosis leads to a successful radiotherapy in a limited range of particles incubation concentration. Macropinocytosis processes in two steps: formation of agglomerates at vicinity of the cell followed by their collect via the lamellipodia (i.e. the "arms") of the cell. The first step is strongly dependent on the physicochemical characteristics of the particles, especially their zeta potential that determines the size of the agglomerates and their distance from the cell. These results should permit to control the quantity of particles internalized in the cell cytoplasm, promising ambitious opportunities towards a particle-assisted radiotherapy using lower radiation doses.
authors.affiliation: INSA-Lyon, MATEIS CNRS UMR5510, 69621 Villeurbanne Cedex, France.
authors.forename: Wael
authors.initials: W
authors.lastname: Rima
authors.forename: Lucie
authors.initials: L
authors.lastname: Sancey
authors.forename: Marie-Thérèse
authors.initials: MT
authors.lastname: Aloy
authors.forename: Emma
authors.initials: E
authors.lastname: Armandy
authors.forename: Gustavo B
authors.initials: GB
authors.lastname: Alcantara
authors.forename: Thierry
authors.initials: T
authors.lastname: Epicier
authors.forename: Annie
authors.initials: A
authors.lastname: Malchère
authors.forename: Lucile
authors.initials: L
authors.lastname: Joly-Pottuz
authors.forename: Pierre
authors.initials: P
authors.lastname: Mowat
authors.forename: François
authors.initials: F
authors.lastname: Lux
authors.forename: Olivier
authors.initials: O
authors.lastname: Tillement
authors.forename: Béatrice
authors.initials: B
authors.lastname: Burdin
authors.forename: Annie
authors.initials: A
authors.lastname: Rivoire
authors.forename: Christelle
authors.initials: C
authors.lastname: Boulé
authors.forename: Isabelle
authors.initials: I
authors.lastname: Anselme-Bertrand
authors.forename: Jérémie
authors.initials: J
authors.lastname: Pourchez
authors.forename: Michèle
authors.initials: M
authors.lastname: Cottier
authors.forename: Stéphane
authors.initials: S
authors.lastname: Roux
authors.forename: Claire
authors.initials: C
authors.lastname: Rodriguez-Lafrasse
authors.forename: Pascal
authors.initials: P
authors.lastname: Perriat
mesh_terms: D045744:Cell Line, Tumor; D002462:Cell Membrane / Q000378:metabolism / Q000648:ultrastructure; D002470:Cell Survival / Q000187:drug effects; D004058:Diffusion; D005682:Gadolinium / Q000378:metabolism*; D006801:Humans; D007700:Kinetics; D053758:Nanoparticles / Q000737:chemistry* / Q000648:ultrastructure; D009369:Neoplasms / Q000378:metabolism* / Q000473:pathology*; D010316:Particle Size; D010873:Pinocytosis; D011554:Pseudopodia / Q000378:metabolism; D011838:Radiation-Sensitizing Agents / Q000378:metabolism*; D013997:Time Factors; D014617:Vacuoles / Q000378:metabolism / Q000648:ultrastructure
chemical_list: D011838:Radiation-Sensitizing Agents; D005682:Gadolinium