H2020Individual fellowship2017–2019

NANOCANCER · Getting new insights into the radio-sensitization effects of nanoparticles in photon and charged particle therapy

Horizon 2020 — Marie Skłodowska-Curie Actions

Duration: 2017-10-30 → 2019-10-29
EU contribution: €158,122
Participants: 1
Scheme: MSCA-IF-EF-SE

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Results in brief

Getting new insights into the radio-sensitization effects of nanoparticles in photon and charged particle therapy

The use of nanoparticles (NP) as dose enhancers in conventional (photon) radiotherapy (RT) is a growing research field. 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. In addition to the damage due to a possible local dose enhancement (physical effects), the interaction of NP with essential biological macromolecules could lead to changes in the cells (biochemical effects) leading to an amplified effect of the radiation. Within this framework, 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. Glioma cells doped with AuNP and GdNP were irradiated using several types of medical ion beams (photons, protons and heavier ions). Differences in cell composition were analyzed in the nucleic acids, protein and lipid spectral regions using Principal Component Analysis (PCA). Results provided new insights into the molecular changes in response to NP-based RT and highlighted the relevance of SR-FTIRM as a useful and precise technique for assessing cell response to innovative radiotherapy approaches. The knowledge of these biochemical features will help researchers to develop RT by taking full advantage of the underlying biology an enhance the therapeutic index of RT for diseases with poor prognosis, such as radioresistant cancers.

Data: CORDIS, © European Union

Project objective

The use of high-atomic-number nanoparticles (NP) as tumour radio-sensitizers has been recently proposed as a breakthrough in radiotherapy (RT). Numerous biological studies have shown the enhanced effectiveness in tumor cell killing when NP were associated to photon RT and, more recently, to charged particle therapy. However, the mechanisms of action are not clear yet. In addition to the damage due to a possible local dose enhancement (physical effects), the interaction of NP with essential biological macromolecules could lead to changes in the cells (biochemical effects) leading to an amplified effect of the radiation. Within this framework, the main goal of the NANOCANCER project is to get deeper insights into the mechanisms underlying the amplification of radiation effects of NP. For this purpose, I will use a multidisciplinary strategy to evaluate both the biochemical and physical effects involved in these innovative nano-RT approaches. Vibrational spectroscopy (Fourier transform infrared, FTIR, microspectroscopy) will be employed for the first time to investigate the biochemical features in glioma cells combining two high-Z standard nanoparticles (Au and Gd) and charged particle beams. Physical effects will be also assessed by performing complementary Monte Carlo simulation of radiation transport, which will allow a realistic modelling of early biological damages induced by the radiation at the nanometre scale. This interdisciplinary proposal will be essential to better characterize the radio-sensitization effects of NP in glioma cells and, in addition, will bring light to the present charged particle therapy radiobiology, which seems to lead to substantially different tumour responses with respect to conventional RT at the cellular and molecular level. The knowledge of these biochemical features will help researchers to develop RT by taking full advantage of the underlying biology an enhance the therapeutic index of RT for diseases with poor prognosis.

Original text from CORDIS.

Participants

CONSORCIO PARA LA CONSTRUCCION EQUIPAMIENTO Y EXPLOTACION DEL LABORATORIO DE LUZ SINCROTRON · Cerdanyola Del Valles BarcelonaCoordinatorSpain

NANOCANCER · Getting new insights into the radio-sensitization effects of nanoparticles in photon and charged particle therapy

Results in brief

Getting new insights into the radio-sensitization effects of nanoparticles in photon and charged particle therapy

Project objective

Participants

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