Internalization pathways into cancer cells of gadolinium-based radiosensitizing nanoparticlesReportar como inadecuado

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* Corresponding author 1 MATEIS - Matériaux, ingénierie et sciences Villeurbanne 2 LPCML - Laboratoire de Physico-Chimie des Matériaux Luminescents 3 EA3738 - Ciblage thérapeutique en Oncologie 4 CTµ - Centre Technologique des Microstructures 5 Centre de Microscopie Electronique Stéphanois 6 IFRESIS-ENSMSE - Institut Fédératif de Recherche en Sciences et Ingénierie de la Santé 7 CIS-ENSMSE - Centre Ingénierie et Santé 8 LINA-ENSMSE - Laboratoire Interdisciplinaire d-Etude des Nanoparticules Aérosolisées 9 Service d-Histologie Embryologie 10 UTINAM - Univers, Transport, Interfaces, Nanostructures, Atmosphère et environnement, Molécules

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 inducein 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.

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

Autor: Wael Rima - Lucie Sancey - Marie-Thérèse Aloy - Emma Armandy - B. Alcantara Gustavo - Thierry Epicier - Annie Malchere - Lucile



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