Internalization pathways into cancer cells of gadolinium-based radiosensitizing nanoparticles

Wael Rima, Lucie Sancey, Marie Thérèse Aloy, Emma Armandy, Gustavo B. Alcantara, Thierry Epicier, Annie Malchère, Lucile Joly-Pottuz, Pierre Mowat, François Lux, Olivier Tillement, Béatrice Burdin, Annie Rivoire, Christelle Boulé, Isabelle Anselme-Bertrand, Jérémie Pourchez, Michèle Cottier, Stéphane Roux, Claire Rodriguez-Lafrasse, Pascal Perriat

Research output: Contribution to journalArticlepeer-review

78 Citations (Scopus)


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.

Original languageEnglish
Pages (from-to)181-195
Number of pages15
Issue number1
Publication statusPublished - 2013 Jan


  • Confocal microscopy
  • Electron microscopy
  • Fluorescence correlation spectroscopy
  • Gadolinium
  • Intracellular localization
  • Radiosensitizing nanoparticles
  • Radiotherapy


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