Motivated by the fundamental need to develop novel nanotechnology-based pathways to achieve relevant performance for biomedical purposes, the Group of Magnetism and Magnetic Materials (GMMM) (UPV / EHU) investigates the use of magnetotactic bacteria as nano-bio-robots (nanobiots) for the fight against cancer.
Magnetotactic bacteria (MTB) are a diverse group of aquatic microorganisms that biomineralize high chemical purity magnetite nanoparticles surrounded by a lipid bilayer membrane with a precise size and morphology due to the genetic control exerted by the bacteria. These membrane-coated nanoparticles are called magnetosomes and are arranged in chains that bacteria use as a compass to orient themselves in Earth's magnetic field. As a consequence, MTB can actively swim due to flagella and passively align along the geomagnetic field. This behavior is known as magnetotaxis. MTBs are microaerobic/anaerobic and have sensory elements that guide them to aquatic areas with their preferred oxygen concentration, a skill called aerotaxis. Due to these characteristics, MTB are envisaged as nano-bio-robots (nanobiots) that can be guided and manipulated by external magnetic fields and are naturally attracted towards hypoxic areas such as tumor regions. Moreover, the presence of the magnetosomes provides the MTB with the biomedical capacities for therapy and imaging attributed to them, such as the ability to heat up under alternating magnetic fields for magnetic hyperthermia therapy.
We are focus on three main aspects:
- Bacterial species. The properties of magnetosomes are specie-specific, it means that different species of magnetotactic bacteria produce magnetite nanoparticles with specific morphology and size. Magnetotactic bacteria are fastidious microorganism difficult to grow in the laboratory but GMMM has a lot of experience in their culture. Currently, the Group steadily cultivates four different magnetotactic bacteria species: Magnetospirillum gryphiswaldense (MSR-1), Magnetospirillum magneticum (AMB-1); Magnetovibrio blakemorei (MV-1) and Magnetococcus marinus (MC-1).
- Fundamental properties. Another aspect is the fundamental study of the magnetic and structural properties of magnetosomes and chains using home techniques and large installations. Magnetosome chains are a natural paradigm of 1D nanostructure that constitutes an incomparable model for studying basic magnetism. Furthermore, an accurate understanding of its magnetic properties is an essential point for proper use in subsequent biomedical applications.
- Biomedical applications. The biocompatibility of magnetosomes and magnetotactic bacteria and the interaction with different cancer cell lines are evaluated through in vitro tests. The Group evaluates the heating efficiency of magnetosomes and magnetic bacteria for hyperthermia treatments and evaluates them as functionalization drug delivery agents.
- In-situ experiments. To test in situ the therapeutic capabilities of bacteria as nanorobots, GMMM is actively working on the design and development of a magnetotaxis platform equipped with an integrated coil system for the control and guidance of bacteria and their subsequent activation by alternating magnetic fields.
A multidisciplinary team, physicists, microbiologists, and electronic engineers are working together in this reaserach line.
Members of the group working on this research line: Mª Luisa Fernández-Gubieda Ruiz, Alicia Muela Blázquez, Ana García Prieto, Alfredo García Arribas, David de Cos, Galina Kurlyandskaya. Post-docs: Maite Goiriena, Lourdes Marcano, Alicia Gascón. Pre-docs: David Gandia, Lucía Gandarias
Selected publication of the last years
Controlled magnetic anisotropy in single domain Mn-doped biosynthesized magnetite nanoparticle, Lourdes Marcano, IñakiOrue, AnaGarcía-Prieto, Radu Abrudan, JavierAlonso, Luis Fernańdez Barquín, Sergio Valencia, Alicia Muela and M. Luisa Fdez-Gubieda, J. Phys. Chem. C 2020, 124, 22827−22838
Perspectives on Magnetotactic bacteria for cancer therapy (invited), Mª Luisa Fernández-Gubieda, J. Alonso, A. García-Prieto, A. García-Arribas, L. Fernandez Barquín, A. Muela, Journal of Applied Physics 128, 070902 (2020)
Magnetosomes could be protective shields against metal stress in magnetotactic bacteria, D. Muñoz, L. Marcano, R. Martín-Rodríguez, L. Simonelli, A. Serrano, A. García-Prieto, M. L. Fdez-Gubieda, A. Muela, Scientific Reports, 10, (2020) 11430
Elucidating the role of shape anisotropy in faceted magnetic nanoparticles using biogenic magnetosomes as a model, David Gandia; Lucía Gandarias, Lourdes Marcano, Iñaki Orue, David Gil-Cartón, Javier Alonso, Alfredo García-Arribas, Alicia Muela, Mª Luisa Fdez-Gubieda, Nanoscale 2020 12, 16081-16090
Disc-shaped magnetic particles for cancer therapy, M. Goiriena-Goikoetxea, D. Muñoz, I. Orue, M.L. Fernandez-Gubieda, J. Bokor, A. Muela, A. García-Arribas; Applied Physics Review (2020) 7, 011306 (2020)
Unlocking the Potential of Magnetotactic Bacteria as Magnetic Hyperthermia Agents; D. Gandia, L. Gandarias, I. Rodrigo, J. Robles-García, R. Das, E. Garaio, J.Á. García, M.H. Phan, H. Srikanth, I. Orue, J. Alonso, A. Muela, M.L. Fdez-Gubieda, Small 2019, 1902626
Magnetic Study of Co-Doped Magnetosome Chains, Marcano, Lourdes; Muñoz, David; Martín-Rodríguez, Rosa; Orue, Iñaki; Alonso, Javier; García-Prieto, Ana; Serrano, Aida; Valencia, Sergio; Abrudan, Radu; Fernandez Barquin, Luis; García-Arribas, Alfredo; Muela, Alicia; Fdez-Gubieda, Mª Luisa; The Journal of Physical Chemistry, 2018, 122, 7541-7550
Configuration of the magnetosome chain: a natural magnetic nanoarchitecture, I. Orue, L. Marcano, P. Bender, A. García-Prieto, S. Valencia, M.A. Mawass,D. Gil-Cartón,7 D. Alba Venero, D. Honecker, A. García-Arribas, L. Fernández Barquín, A. Muela, M.L. Fdez-Gubieda; Nanoscale, 2018, 10, 7407-7419
Influence of the bacterial growth phase on the magnetic properties of magnetosomes synthesized by Magnetospirillum gryphiswaldense; L. Marcano, A. García-Prieto, D. Muñoz, L. Fernández Barquín, I. Orue, J. Alonso, A. Muela, M.L. Fdez-Gubieda; Biochimica et Biophysica Acta, Volume 1861, Issue 6, June 2017, Pages 1507-1514
Optimal Parameters for Hyperthermia Treatment Using Biomineralized Magnetite Nanoparticles: Theoretical and Experimental Approach; Alicia Muela, David Muñoz, Rosa Martín-Rodríguez, Iñaki Orue, Eneko Garaio, Ana Abad Díaz de Cerio, Javier Alonso, José Ángel García, and M. Luisa Fdez-Gubieda; J. Phys. Chem. C 2016, 120, 24437-24448
On the mineral core of ferritin-like proteins: structural and magnetic characterization;García-Prieto, Ana; Alonso, J; D. Muñoz; L. Marcano, A. Abad Díaz de Cerio, R. Fernández de Luis, Orue, Inaki; O. Mathon; A. Muela; Fernandez-Gubieda, Maria Luisa, Nanoscale (2016) vol. 8 pp. 1088 (Impact Factor: 7.394)
Assemblies of magnetite nanoparticles extracted from magnetotactic bacteria: a magnetic study; A. M. Huízar-Felix, D. Muñoz, I. Orue, C. Magén, A. Ibarra, J. M. Barandiarán, A. Muela, and M. L. Fdez-Gubieda; APPLIED PHYSICS LETTERS 108, 063109 (2016)
Magnetite biomineralization in Magnetospirillum gryphiswaldense: time-resolved magnetic and structural studies, M. Luisa Fdez-Gubieda, Alicia Muela, Javier Alonso, Ana García-Prieto, Luca Olivi, Rodrigo Fernández-Pacheco, and José Manuel Barandiarán, ACS Nano, vol.7, n.4, 3297-3305 (2013)