Periodic Reporting for period 1 - ProteNano-MAG (Eco-friendly and bioinspired protein-based synthesis of magnetic nanomaterials for advanced cancer theranostics)
Período documentado: 2023-06-01 hasta 2026-05-31
The ProteNano-MAG project vision encompasses the creation of eco-friendly and bioinspired protein-based magnetic nanomaterials designed to improve the diagnosis and treatment of cancer, one of the most pressing health challenges worldwide. Cancer remains the second leading cause of death globally, and despite great advances in therapy and early detection, there is an urgent need for more efficient, sensitive, selective, and sustainable biomedical tools. ProteNano-MAG brings together nanotechnology, protein engineering, and biomedical sciences to develop green synthesis routes for magnetic nanoparticles that are safe for patients and environmentally responsible in their production.
The project draws inspiration from magnetotactic bacteria, microorganisms capable of producing highly uniform magnetic crystals known as magnetosomes. These natural nanoparticles exhibit outstanding magnetic and structural properties because their formation is guided by specialised proteins. ProteNano-MAG translates this biological precision into an artificial but sustainable system: engineered proteins act as templates that replicate the natural mineralisation process under mild, eco-friendly conditions. By combining biological design principles with nanofabrication, the project demonstrates how materials can be produced without toxic reagents or extreme processing, aligning with the European Green Deal and the Sustainable Development Goals.
This innovative approach advances the field of nanomedicine by generating magnetic nanoparticles that can perform dual diagnostic and therapeutic functions. The resulting nanomaterials are expected to have potential to enhance MRI image quality, deliver drugs to specific tumour sites, and generate localised heat under an alternating magnetic field to kill cancer cells, three key functionalities for future personalised medicine.
The objectives of ProteNano-MAG are:
1. To design and optimise engineered proteins based on the consensus tetratricopeptide repeat (CTPR) scaffold to guide the synthesis of iron-oxide/protein nanohybrids with sizes around 5 nm, suitable as positive contrast agents for Magnetic Resonance Imaging (MRI) and as multifunctional therapeutic platforms.
2. To develop bioinspired synthesis routes that mimic the natural formation of magnetosomes in bacteria by using synthetic nanoreactors such as lipid vesicles, enabling the controlled preparation of single-domain magnetic nanoparticles with high purity and magnetic performance.
3. To control and tune nanoparticle morphology through protein design, identifying the shapes and magnetic characteristics that maximise heating efficiency for cancer hyperthermia applications.
ProteNano-MAG contributes to the EU’s mission to promote responsible, sustainable, and socially relevant innovation in healthcare. By demonstrating that high-performance nanomaterials can be produced through green and bioinspired approaches, the project opens new avenues for environmentally conscious nanotechnology and strengthens Europe’s leadership in next-generation biomedical research.
The project draws inspiration from magnetotactic bacteria, microorganisms capable of producing highly uniform magnetic crystals known as magnetosomes. These natural nanoparticles exhibit outstanding magnetic and structural properties because their formation is guided by specialised proteins. ProteNano-MAG translates this biological precision into an artificial but sustainable system: engineered proteins act as templates that replicate the natural mineralisation process under mild, eco-friendly conditions. By combining biological design principles with nanofabrication, the project demonstrates how materials can be produced without toxic reagents or extreme processing, aligning with the European Green Deal and the Sustainable Development Goals.
This innovative approach advances the field of nanomedicine by generating magnetic nanoparticles that can perform dual diagnostic and therapeutic functions. The resulting nanomaterials are expected to have potential to enhance MRI image quality, deliver drugs to specific tumour sites, and generate localised heat under an alternating magnetic field to kill cancer cells, three key functionalities for future personalised medicine.
The objectives of ProteNano-MAG are:
1. To design and optimise engineered proteins based on the consensus tetratricopeptide repeat (CTPR) scaffold to guide the synthesis of iron-oxide/protein nanohybrids with sizes around 5 nm, suitable as positive contrast agents for Magnetic Resonance Imaging (MRI) and as multifunctional therapeutic platforms.
2. To develop bioinspired synthesis routes that mimic the natural formation of magnetosomes in bacteria by using synthetic nanoreactors such as lipid vesicles, enabling the controlled preparation of single-domain magnetic nanoparticles with high purity and magnetic performance.
3. To control and tune nanoparticle morphology through protein design, identifying the shapes and magnetic characteristics that maximise heating efficiency for cancer hyperthermia applications.
ProteNano-MAG contributes to the EU’s mission to promote responsible, sustainable, and socially relevant innovation in healthcare. By demonstrating that high-performance nanomaterials can be produced through green and bioinspired approaches, the project opens new avenues for environmentally conscious nanotechnology and strengthens Europe’s leadership in next-generation biomedical research.
The main results from the work performed during the reporting period along the different WPs are:
(WP1) Scientific, technical and complementary training
The researcher received advanced training in protein engineering, molecular biology and nanomaterials design at CIC biomaGUNE. She learned protein design, overexpression and purification of engineered CTPR scaffolds, applying standard characterisation techniques (DLS, CD, ICP-MS, TEM) and combining them with her previous expertise in magnetism and synchrotron methods (AC magnetometry, XANES/EXAFS). Complementary training in project management, teaching and communication was completed, fulfilling all career development milestones.
(WP2) Fabrication and optimisation of iron oxide/protein nanohybrids
CTPR proteins were successfully used as templates for the green synthesis of Fe-based nanohybrids. The materials showed superparamagnetic behaviour, good colloidal stability and promising MRI contrast performance. Synchrotron studies (ALBA) confirmed controlled Fe coordination, validating the bioinspired synthesis. Additional Au–protein clusters exhibiting fluorescence were also obtained, opening possibilities for multimodal imaging.
(WP3) Bioinspired green synthesis of single-domain MNPs
The biomineralization process in magnetotactic bacteria was investigated to understand magnetite formation. In parallel, lipid-based nanoreactors were developed to mimic bacterial vesicles. Preliminary results suggest their suitability for confined, protein-mediated nanoparticle synthesis under mild conditions.
(WP4) Morphology modification and magnetic hyperthermia
Collaborative studies on magnetotactic bacteria provided insights into the link between nanoparticle morphology, magnetic anisotropy and heating efficiency, relevant for hyperthermia applications.
(WP5) Management and outcomes
The researcher published six papers and one book chapter, conducted two synchrotron experiments, and participated in international collaborations and outreach activities. The fellowship strengthened her interdisciplinary profile and established a proof of concept for sustainable, bioinspired synthesis of magnetic nanomaterials for cancer theranostics.
(WP1) Scientific, technical and complementary training
The researcher received advanced training in protein engineering, molecular biology and nanomaterials design at CIC biomaGUNE. She learned protein design, overexpression and purification of engineered CTPR scaffolds, applying standard characterisation techniques (DLS, CD, ICP-MS, TEM) and combining them with her previous expertise in magnetism and synchrotron methods (AC magnetometry, XANES/EXAFS). Complementary training in project management, teaching and communication was completed, fulfilling all career development milestones.
(WP2) Fabrication and optimisation of iron oxide/protein nanohybrids
CTPR proteins were successfully used as templates for the green synthesis of Fe-based nanohybrids. The materials showed superparamagnetic behaviour, good colloidal stability and promising MRI contrast performance. Synchrotron studies (ALBA) confirmed controlled Fe coordination, validating the bioinspired synthesis. Additional Au–protein clusters exhibiting fluorescence were also obtained, opening possibilities for multimodal imaging.
(WP3) Bioinspired green synthesis of single-domain MNPs
The biomineralization process in magnetotactic bacteria was investigated to understand magnetite formation. In parallel, lipid-based nanoreactors were developed to mimic bacterial vesicles. Preliminary results suggest their suitability for confined, protein-mediated nanoparticle synthesis under mild conditions.
(WP4) Morphology modification and magnetic hyperthermia
Collaborative studies on magnetotactic bacteria provided insights into the link between nanoparticle morphology, magnetic anisotropy and heating efficiency, relevant for hyperthermia applications.
(WP5) Management and outcomes
The researcher published six papers and one book chapter, conducted two synchrotron experiments, and participated in international collaborations and outreach activities. The fellowship strengthened her interdisciplinary profile and established a proof of concept for sustainable, bioinspired synthesis of magnetic nanomaterials for cancer theranostics.
Results in WP2 demonstrate that engineered CTPR proteins can act as efficient, tunable templates for the green synthesis of magnetic and hybrid nanomaterials. The project achieved the controlled formation of stable Fe-based nanohybrids under eco-friendly conditions that evidences magnetic behaviour. These results open avenues for biocompatible, sustainable and multifunctional nanoplatforms for diagnosis and therapy.
Results in WP3 are in the way to confirm the feasibility of mimicking bacterial biomineralization through synthetic lipid nanoreactors that replicate the vesicular environment of magnetotactic bacteria. This represents a conceptual and methodological advance over existing chemical routes, introducing a biocompatible confinement system to control crystal growth. Understanding the mechanisms of natural magnetite formation also bridges microbiology and nanotechnology, creating a foundation for rational design of magnetic nanoparticles with optimised magnetic response.
Results in WP4, derived from collaborative studies on magnetotactic bacteria, establish a link between nanoparticle morphology, magnetic anisotropy and heat generation efficiency. These findings advance the understanding of magnetic hyperthermia mechanisms at the nanoscale and provide valuable guidance for engineering artificial magnetic systems for cancer treatment with optimised heating performance.
Overall, ProteNano-MAG advances the state of the art by demonstrating that engineered proteins can replace harsh chemical conditions in nanoparticle synthesis, introducing a sustainable alternative with biomedical potential. Further development could involve scaling up the synthesis, testing biocompatibility and therapeutic efficiency in vivo, and pursuing patent protection and industrial partnerships for translation. Support in IPR management, regulatory alignment, and targeted funding will be key to transform these proof-of-concept results into viable applications in clinical nanomedicine and green materials manufacturing.
Results in WP3 are in the way to confirm the feasibility of mimicking bacterial biomineralization through synthetic lipid nanoreactors that replicate the vesicular environment of magnetotactic bacteria. This represents a conceptual and methodological advance over existing chemical routes, introducing a biocompatible confinement system to control crystal growth. Understanding the mechanisms of natural magnetite formation also bridges microbiology and nanotechnology, creating a foundation for rational design of magnetic nanoparticles with optimised magnetic response.
Results in WP4, derived from collaborative studies on magnetotactic bacteria, establish a link between nanoparticle morphology, magnetic anisotropy and heat generation efficiency. These findings advance the understanding of magnetic hyperthermia mechanisms at the nanoscale and provide valuable guidance for engineering artificial magnetic systems for cancer treatment with optimised heating performance.
Overall, ProteNano-MAG advances the state of the art by demonstrating that engineered proteins can replace harsh chemical conditions in nanoparticle synthesis, introducing a sustainable alternative with biomedical potential. Further development could involve scaling up the synthesis, testing biocompatibility and therapeutic efficiency in vivo, and pursuing patent protection and industrial partnerships for translation. Support in IPR management, regulatory alignment, and targeted funding will be key to transform these proof-of-concept results into viable applications in clinical nanomedicine and green materials manufacturing.