Speaker
Description
Glioblastoma (GBM) is among the most aggressive and heterogeneous human cancers, characterized by complex molecular alterations, extensive cellular diversity, and limited therapeutic options. Understanding GBM progression and treatment response requires analytical approaches capable of connecting molecular composition with cellular organization and tissue-like complexity across multiple biological scales.
In this work, we demonstrate the potential of complementary synchrotron-based imaging and spectroscopy approaches to investigate glioblastoma from single cells to three-dimensional (3D) tumor models, including multicellular spheroids and organoid systems. X-ray fluorescence imaging, soft X-ray microscopy, and synchrotron radiation-based FTIR (SR-FTIR) spectromicroscopy were combined to characterize elemental distribution, cellular ultrastructure, and biochemical composition in near-native conditions. These multimodal approaches revealed tumor-associated alterations in elemental homeostasis, cytoskeletal organization, and key biomolecular components, including proteins, lipids, and nucleic acids, providing new insights into GBM heterogeneity across different biological scales.
Synchrotron-based methods were further applied to investigate a nanomedicine strategy using carbon dots derived from 2-acrylamido-2-methylpropanesulfonic acid (AMPS-CDs) as a delivery platform for riluzole, a compound with potential anticancer activity. Comprehensive characterization using FTIR, XPS, NMR spectroscopy, and cryo-transmission electron microscopy demonstrated the surface chemistry and functional groups responsible for the nanoparticles’ biocompatibility and drug-loading capability. The AMPS-CDs@riluzole system enhanced selective cytotoxic effects in GBM cells while maintaining low toxicity of the carrier itself.
Live-cell SR-FTIR microspectroscopy enabled in situ monitoring of molecular responses following treatment, revealing alterations in DNA, protein secondary structures, and lipid metabolism. Extending these studies from conventional cell models toward 3D spheroids and organoids provides a more physiologically relevant platform to investigate tumor architecture, microenvironmental effects, and therapeutic responses.
By integrating synchrotron-based structural, chemical, and imaging approaches across multiple length scales—from molecules and organelles to single cells and 3D tumor models—this work highlights the unique capability of synchrotron facilities to advance mechanistic understanding of cancer biology, identify molecular biomarkers, and support the development of targeted therapeutic strategies in precision oncology.
- Dučić, T., Pereiro, E., Ninkovic, M., Sperling, S., Rohde, V.,
Fernández-González, C., Algarra, M., González-Muñoz, E., 2025,
Journal of Nanobiotechnology, 23(1):629.
https://doi.org/10.1186/s12951-025-03687-2 - Algarra, M., et al., 2024, ACS Omega, 9(12):13818–13830. https://doi.org/10.1021/acsomega.3c08459
- Dučić, T., et al., 2026. 3D Glioblastoma Molecular Responses to Carbon Dot–Delivered Riluzole Probed by Synchrotron FTIR. Analytical
Chemistry, 98(17), 12775–12789.
https://doi.org/10.1021/acs.analchem.6c00176