Study of the intracellular nanoparticle-based radiosensitization mechanisms in F98 glioma cells treated with charged particle therapy through synchrotron-based infrared microspectroscopy

• Published in: Analyst (London) Vol. 145; no. 6; pp. 2345 - 2356
• Main Authors: Martínez-Rovira, I, Seksek, O, Dokic, I, Brons, S, Abdollahi, A, Yousef, I
• Format: Journal Article
• Language: English
• Published: England Royal Society of Chemistry 16.03.2020
• Subjects: Animals; Banded structure; Cell Line, Tumor; Cellular structure; Charged particles; Damage; Deoxyribonucleic acid; DNA; Fourier transforms; Gadolinium - chemistry; Gadolinium - radiation effects; Infrared analysis; Infrared spectroscopy; Ion beams; Light; Lipids; Lipids - chemistry; Metal Nanoparticles - chemistry; Metal Nanoparticles - radiation effects; Microspectrophotometry - methods; Microspectrophotometry - statistics & numerical data; Nanoparticles; Nucleic Acid Conformation - drug effects; Nucleic acids; Nucleic Acids - chemistry; Nucleic Acids - drug effects; Performance enhancement; Principal Component Analysis; Principal components analysis; Protein Conformation - drug effects; Proteins; Proteins - chemistry; Proteins - drug effects; Radiation therapy; Radiation-Sensitizing Agents - pharmacology; Radiation-Sensitizing Agents - radiation effects; Rats; Silver - chemistry; Silver - radiation effects; Synchrotrons
• ISSN: 0003-2654; 1364-5528
• DOI: 10.1039/c9an02350j

The use of nanoparticles (NP) as dose enhancers in radiotherapy (RT) is a growing research field. Recently, the use of NP has been extended to charged particle therapy in order to improve the performance in radioresistant tumors. However, the biological mechanisms underlying the synergistic effects involved in NP-RT approaches are not clearly understood. Here, we used the capabilities of synchrotron-based Fourier Transform Infrared Microspectroscopy (SR-FTIRM) as a bio-analytical tool to elucidate the NP-induced cellular damage at the molecular level and at a single-cell scale. F98 glioma cells doped with AuNP and GdNP were irradiated using several types of medical ion beams (proton, helium, carbon and oxygen). Differences in cell composition were analyzed in the nucleic acids, protein and lipid spectral regions using multivariate methods (Principal Component Analysis, PCA). Several NP-induced cellular modifications were detected, such as conformational changes in secondary protein structures, intensity variations in the lipid CH x stretching bands, as well as complex DNA rearrangements following charged particle therapy irradiations. These spectral features seem to be correlated with the already shown enhancement both in the DNA damage response and in the reactive oxygen species (ROS) production by the NP, which causes cell damage in the form of protein, lipid, and/or DNA oxidations. Vibrational features were NP-dependent due to the NP heterogeneous radiosensitization capability. Our results provided new insights into the molecular changes in response to NP-based RT treatments using ion beams, and highlighted the relevance of SR-FTIRM as a useful and precise technique for assessing cell response to innovative radiotherapy approaches. This work provides new insights into the molecular changes in response to nanoparticle-based radiotherapy treatments using ion beams through synchrotron-based infrared microspectroscopy.