The main scientific objective of the project was to get deeper insights into the radiosensitization mechanisms underlying the amplification of radiation effects of (Au and Gd) NP in glioma cells. Specifically, the radiosensitization effects were evaluated under several type of radiations: megavoltage RT using photons and charged particle RT.
MEGAVOLTAGE RT
The main goal of this part was to provide new insights into the radiosensitization effects of glioma cells exposed to gadolinium and gold NP combined with clinical megavoltage beams and compare them with respect to kilovoltage RT (commonly used in combination with NP). For this purpose, we used SR-FTIRM to provide relevant information on the treatment-induced biochemical changes of the main cell biomolecules.
PCA revealed Gadolinium NP-dependent changes in megavoltage treated cells. However, PCA did not discriminate clearly between megavoltage and kilovoltage groups treated with NP, indicating that megavoltage radiosensitization effects might not differ significantly from those in kilovoltage RT.
Gold NP (AuNP) have become particularly popular due to their multiple advantages. Within this context, our research work also aimed to study the biochemical radiosensitization capacity of F98 and U87-MG glioma cell lines to AuNP combined with X-ray irradiations through SR-FTIRM. SR-FTIRM data revealed clear AuNP-induced changes in the DNA, protein and lipid spectral regions.
More scientific details can be found in the related Gold Open Access publications:
• Martínez-Rovira et al. Analyst 144, 5511-5520 (2019). DOI: 10.1039/C9AN00792J.
• Martínez-Rovira et al. Analyst 144, 6352-6364 (2019). DOI: 10.1039/C9AN01109A.
Our works constituted the first studies that evaluates cell radiosensitization to nanoparticles by using SR-FTIRM, providing the foundation for understanding the cell changes in response to NP-based RT treatments. Our studies also highlighted the relevance of SR-FTIRM as a useful and precise technique for assessing cell response to innovative RT approaches.
CHARGED PARTICLE RT
Recently, the use of NP has been extended to charged particle RT in order to improve the performance in very radioresistant tumors. However, the biological mechanisms underlying the synergistic effects involved in NP-RT approaches are not clearly understood. Within this context, we used the capabilities of SR-FTIRM as a bio-analytical tool to elucidate the NP-induced cellular damage at the molecular level and at a single-cell scale in charged particle RT.
F98 glioma cells doped with AuNP and GdNP were irradiated using several types of medical ion beams. Differences in cell composition were analyzed in the nucleic acids, protein and lipid spectral regions using PCA. Several NP-induced cellular modifications were detected, which seem to be correlated to 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.
An article has been recently submitted for publication:
• Martínez-Rovira et al. "Charged particle therapy and nanoparticles: study of the F98 glioma cells radiosensitization mechanisms at the molecular level through synchrotron-based infrared microspectroscopy".
This study constituted the first work that evaluates cell radiosensitization to NP in charged particle RT by using SR-FTIRM, providing new insights into the understanding of the cell response to NP-based charged particle RT treatments.
DISSEMINATION ACTIVITIES
Dissemination activities took place in order to give the maximum visibility of the goals, outcome and expected impact of the project. The dissemination method to specialized public included scientific publications (described previously) and the participation in scientific conferences (PTCOG, IUPESM, etc.).
Results were also published in the ALBA website. They present a regular review of ALBA synchrotron news, updates and developments and will reach specialized and non-specialized audiences.
Finally, to create awareness of the importance of research to society, we were committed to celebrate outreach activities to non-specialized public related with this project. Among the possible activities that serve to disseminate the importance of this proposal to a larger audience, I focused on performing outreach research presentations to undergraduate students in order to promote science among young students.
