
Research Projects


Call: Proyectos de Consolidación Investigadora 2023
Budget: 126 400 €
2024-2026
PI: Raluca Fratila


CALYPSO - LoCALized magnetic hYPerthermia for direct intracellular delivery to avoid endoSOmal entrapment
Magnetic nanoparticles (MNPs) are able to absorb energy from an external alternating magnetic fields (AMF) and convert it into heat, behaving as nanoheaters. CALYPSO will use localised magnetic heating to induce transient changes in the fluidity and permeability of the plasma membrane and promote direct intracellular delivery of materials, overcoming traditional endocytosis pathways and avoiding endosomal entrapment. To do so, CALYPSO proposes the use of immobilised on the plasma membrane of living cells in a covalent manner through bioorthogonal chemistry. This strategy will ensure that the heating remains localised to the plasma membrane. The CALYPSO approach will be validated in vitro in different cell lines using nanomaterials and cell-impermeable fluorescent probes.
Nano4Zombie - Senolytic nanoplatform to target and eliminate skin cancer Zombie cells
Ageing leads to an increase in senescent cells (SCs), which can contribute to tumorigenesis. Elimination of cancer-associated SCs is a new promising approach to prevent or delay cancer recurrence. However, many senolytic drugs have shown adverse effects at high doses in clinical trials or low activity. Novel strategies to increase selectivity, bioavailability and activity are needed in order to enhance the effectiveness and safety.
The aims of Nano4Zombie are to: i) Develop new quercetin derivatives with improved action towards cancer SCs; ii) Develop a nanoplatform to eradicate skin cancer SCs by combining magnetic hyperthermia and senolytic drugs. iii) Analyse the functional effects of SC-derived extracellular vesicles released from treated and untreated skin cancer SC son cells constituting the tumour microenvironment.



Call: Proyectos de Generación de Conocimiento 2021
Budget: 168 190 €
2022-2025
PI: María Moros & Raluca Fratila
GALACTIC - Remote GAting of Piezo1 channeLs with mAgnetiC nanoparTICle actuators
Mechanotransduction alludes to the processes through which cells sense these mechanical forces from the environment and convert them into biochemical signals, triggering specific cellular responses. Magnetic nanoparticles (MNPs) are an attractive option for mechanotransduction due to their capability to control mechanical forces via an external magnetic field. GALACTIC will develop a new platform to investigate the remote and spatiotemporal activation of Piezo1, a key mechanosensory channel, using different configurations of magnetic field applicators to activate MNPs targeted to the cellular membrane.

Call: H2020-NMBP-TO-IND
Budget: 8 480 543 €
(503 000 € UNIZAR)
2019-2023
PI UNIZAR: Raluca Fratila
TBMED -An Open Innovation test bed for the development of high-risk medical devices
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TBMED aims to develop an Open Innovation Test Bed (OITB) for high risk medical devices that provides a single entry point to services along the whole value chain from preclinical development to clinical testing. The entire development will be based on a Quality-by-Design (QbD) concept.
In TBMED, we work on the development of a synergistic magnetic hyperthermia-chemotherapy approach for pancreatic cancer treatment. A new manufacturing process of magnetic nanoparticles is being developed using the QbD approach, based on more reproducible and easily scalable methods in order to validate the manufacturing process to regulatory requirements.

Call: M-ERA.NET 2016
Budget: 337.313 €
2017-2021
PI : Valeria Grazú
MagicCELLGene - Localized MAGnetiC hyperthermia CELL-based GENE therapy for immune modulation
The goal of MagicCELLGene is to develop a novel, universal and highly efficient methodology for transfection triggered by magnetic hyperthermia, with potential clinical applications in cell-based gene therapy. Our innovative approach is to induce a controlled and localized heating of the cellular membrane (hotspots) using magnetic nanoparticles covalently immobilized onto cell membranes via bioorthogonal chemistry; the reversible changes of the cell membrane permeability/fluidity will be used to promote the artificial delivery of nucleic acids into cells. Efforts will be especially focused on hard-to-transfect cells (primary cells), thus clearly addressing an unmet need of the transfection market. Expected results going beyond the state-of-the-art in transfection are: i) the development of a universal transfection tool and ii) its application to systems where standard transfection methods have several bottlenecks using as a model immune system modulation.​

Call: PGC 2018
Budget: 72 600 €
2019-2022
PI : Raluca Fratila & Lucía Gutiérrez



MACBETH - Magnetic nanoparticles for cell membrane hyperfluidization with localized hyperthermia
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With the MACBETH project, we aim at generating a protocol to modify the cell membrane fluidity through the use of magnetic nanoparticles (MNPs) covalently bound to the cell membrane and remotely activated by alternating magnetic fields (magnetic hyperthermia, MH) or near infrared light (optical hyperthermia, OH). This approach will allow us to:
1) Explore the different hyperthermia approaches (either MH or OH) as tools for the
hyperfluidization of the cellular membrane of living cells;
2) Study the effect that this increased cell membrane fluidity has on the cellular internalization of MNPs, both in terms of efficiency and intracellular localization of the MNPs.
3) Evaluate the cell membrane hyperfluidization as a potential tool for enhancing cellular uptake of MNPs in tumoral cells with low MNP internalization in normal conditions.


Call: MSCA-IF-2014
Budget: 158 121 €
2015-2017
PI : Raluca Fratila
OUTstandINg - Cell-surface immobilized vs. internalized magnetic nanoparticles for magnetic hyperthermia studies
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The MSC OUTstandINg project will use bioorthogonal click chemistry as tool to covalently attach magnetic nanoparticles (MNPs) to living cell surfaces with the aim to address two fundamental questions in the field of magnetic hyperthermia therapy using MNPs: 1) how the subcellular localization (on the plasma membrane or inside the cells) of MNPs affects their heating behaviour when compared to MNPs in solution 2) how MNPs immobilization and sub-lethal magnetic hyperthermia impact different subcellular signalling pathways and the biophysics of cell membranes.
OUTstandINg is a multidisciplinary two-years research project built upon the expertise of the Fellow (Dr. Raluca M. Fratila) in bioorganic chemistry (including click chemistry, bioconjugates and functionalization of surfaces and (nano)materials) and the experience of the supervisor (Dr. Jesús Martínez de la Fuente) and of the host group (GN2 - Nanotherapy and Nanobiosensors, University of Zaragoza, Spain) in nanotechnology and nanomedicine. This MSC action will offer the Fellow the possibility to work in one of the top European institutions in nanoscience, where she will further develop her skills and will acquire new skills and knowledge necessary for the progress of her scientific career towards an independent position. The secondment period at University College London Institute for Biomedical Engineering (supervisor Prof. Quentin Pankhurst) will reinforce and complete the multidisciplinary training-through-research. The project will generate important knowledge and collaborations in the European Research Area (ERA) and will contribute to enhance the excellence of ERA through cutting-edge research at the frontier of chemistry, physics, materials science, cell biology and nanotechnology.