Sarcoma cell-specific radiation sensitization by titanate scrolled nanosheets: insights from physicochemical analysis and transcriptomic profiling

钛酸盐卷绕纳米片对肉瘤细胞特异性放射增敏作用:从物理化学分析和转录组分析中获得的见解

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作者:Pierre Beaudier #, Florent Vilotte #, Marina Simon #, Giovanna Muggiolu #, Quentin Le Trequesser, Guillaume Devès, Laurent Plawinski, Antoine Mikael, Jérôme Caron, Guy Kantor, Denis Dupuy, Marie-Hélène Delville, Philippe Barberet, Hervé Seznec

Abstract

This study aimed to explore the potential of metal oxides such as Titanate Scrolled Nanosheets (TNs) in improving the radiosensitivity of sarcoma cell lines. Enhancing the response of cancer cells to radiation therapy is crucial, and one promising approach involves utilizing metal oxide nanoparticles. We focused on the impact of exposing two human sarcoma cell lines to both TNs and ionizing radiation (IR). Our research was prompted by previous in vitro toxicity assessments, revealing a correlation between TNs' toxicity and alterations in intracellular calcium homeostasis. A hydrothermal process using titanium dioxide powder in an alkaline solution produced the TNs. Our study quantified the intracellular content of TNs and analyzed their impact on radiation-induced responses. This assessment encompassed PIXE analysis, cell proliferation, and transcriptomic analysis. We observed that sarcoma cells internalized TNs, causing alterations in intracellular calcium homeostasis. We also found that irradiation influence intracellular calcium levels. Transcriptomic analysis revealed marked disparities in the gene expression patterns between the two sarcoma cell lines, suggesting a potential cell-line-dependent nano-sensitization to IR. These results significantly advance our comprehension of the interplay between TNs, IR, and cancer cells, promising potential enhancement of radiation therapy efficiency.

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