Cerdanyola del Vallès, 3rd October 2019. The use of nanotechnology in medicine is nothing short of revolutionary. Nanosensors for diagnosis, nanoparticles for drug delivery or nanodevices that can regenerate damaged tissue are changing the way we face and treat several diseases.
Combining radiotherapy with nanoparticles is a promising strategy to increase the efficacy of cancer treatments. High-atomic number nanoparticles are used as tumour radiosensitizers: tumour cells previously loaded with nanoparticles enhance the radiation effects when exposed to radiotherapy. "It's a kind of knock-on effect; the interaction of the radiation with the nanoparticles generates short-range secondary radiation that induces a local dose enhancement in the tumour cells. However, the mechanisms underlying the synergistic effects involved in these techniques are not clearly understood', says Immaculada Martínez-Rovira, Marie Curie scientist of ALBA and expert in the development of innovative radiotherapy approaches.
A research team from ALBA Synchrotron in collaboration with the Hospital Universitari Sant Joan de Reus has analysed the molecular effects induced by gadolinium and gold nanoparticles combined with different types of radiotherapy on glioma cells. Gliomas are one of the most aggressive brain tumours rarely curable. "With this combined therapy, higher treatment doses could be applied in the tumour, while sparing the surrounding healthy tissue", continues I. Martínez-Rovira.
Using the MIRAS beamline of the ALBA Synchrotron, researchers could study the biochemical changes induced by these novel nanoparticle-based radiotherapy approaches at the single-cell level. "Synchrotron-based infrared microspectroscopy is a technique that allows to identify the chemical composition and structure of molecules vibration, so it is of great help in biomedical studies like this one. Indeed, the use of infrared is key as it does not cause any damage on cells, making possible to know what happens inside them", says Ibraheem Yousef, scientist in charge of the MIRAS beamline at ALBA.
The main results of the experiment have been recently published in two articles, concluding that several nanoparticle-induced cellular modifications were detected in the main biomolecules: proteins, lipids and nucleic acids. The biochemical alterations observed in this work provided key information on the specific nanoparticle radiosensitization action as a function of the radiotherapy approach, nanoparticle type and cell line.
"There is still a long way to go and further research is needed in this growing research field. Deciphering the underlying biological mechanisms behind these radiotherapy techniques is an important step to improve radiotherapy treatments for diseases with poor prognosis", says I. Martínez-Rovira.
This research is part of the European funded project NANOCANCER (grant agreement ID 748889), a Marie Skłodowska-Curie Individual Fellowship, aimed at getting deeper insights into the mechanisms underlying the amplification of radiation effects of nanoparticles, both in conventional and in charged particle therapy.
Researchers from the MIRAS beamline, the Hospital Universitari Sant Joan de Reus (Institut d'Investigació Sanitària Pere Virgili), the Laboratoire d'Imagerie et Modélisation en Neurobiologie et Cancérologie (French National Research Centre for Scientific Research) and the Ionizing Research Group of the Universitat Autònoma de Barcelona (UAB) participated in this research study.
Researchers Imma Martínez-Rovira, Marie Curie scientist of ALBA and expert in the development of innovative radiotherapy approaches, and Ibraheem Yousef, scientist in charge of the MIRAS beamline at the ALBA Synchrotron.
Fig: Savitzky–Golay second derivative of the averaged absorbance spectra for controls, megavoltage (MV) and kilovoltage (kV) radiotherapy in the presence (+NP) and absence (-NP) of Gd nanoparticles (GdNP). The GdNP-induced biochemical modifications give us new insights into the radiosensitization action of these nanoparticles in F98 glioma cells.
References
• I. Martínez-Rovira et al. "Synchrotron-based infrared microspectroscopy study on the radiosensitization effects of Gd nanoparticles at megavoltage radiation energies" Analyst 144, 5511-5520 (2019). DOI: 10.1039/C9AN00792J.
• I. Martínez-Rovira et al. "A synchrotron-based infrared microspectroscopy study on the cellular response induced by gold nanoparticles combined with x-ray irradiations on F98 and U87-MG glioma cell lines" Analyst (2019). DOI: 10.1039/C9AN01109A.
