Internalization pathways into cancer cells of gadolinium-based radiosensitizing nanoparticles

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• 作者：Wael Rima^a ; Lucie Sancey^b ; Marie-Thé ; rè ; se Aloy^c ; Emma Armandy^c ; Gustavo B. Alcantara^a ; Thierry Epicier^a ; Annie Malchè ; re^a ; Lucile Joly-Pottuz^a ; Pierre Mowat^b ; Franç ; ois Lux^b ; Olivier Tillement^b ; Bé ; atrice Burdin^d ; Annie Rivoire^d ; Christelle Boulé ; ^d ; Isabelle Anselme-Bertrand^e ; Jé ; ré ; mie Pourchez^f ; Michè ; le Cottier^g ; Sté ; phane Roux^h ; Claire Rodriguez-Lafrasse^c ; Pascal Perriat^a ; ^{pascal.perriat@insa-lyon.fr}
• 关键词：Gadolinium ; Radiosensitizing nanoparticles ; Intracellular localization ; Radiotherapy ; Fluorescence correlation spectroscopy ; Electron microscopy ; Confocal microscopy
• 刊名：Biomaterials
• 出版年：2013
• 出版时间：January, 2013
• 年：2013
• 卷：34
• 期：1
• 页码：181-195
• 全文大小：1955 K

文摘

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.