The use of nanoscale structures has been used by Nature for billions of years. Two properties that make them very interesting for use in biomedical applications are (i) they have a typical size similar to biological components and (ii) the possibility of manipulating and designing materials with almost à la carte properties controlling the size, composition and shape. The research of our group is mainly focused on the use of magnetic nanoparticles and their ability to generate heat applying an alternating magnetic field. For that, different iron oxides nanoparticles has been prepared by different methodologies and with different size and organic or inorganic coatings. The potential of using the generated heat by applying alternating magnetic fields in the microenvironment of magnetic nanoparticles to activate multienzymatic industrial bioprocesses has been explored. This feature will be also used for the treatment of cancer by magnetic hyperthermia or targeted enzyme therapy. Our research is divided into two distinct but clearly related fields through a common nexus: the type of material used to generate heat by applying an alternating magnetic field (magnetic nanoparticles). 1) Magnetic Hyperthermia for Biocatalysis: We report here how the properties of magnetic nanoparticles (NPs) and of thermophilic enzymes can be combined to obtain NP-enzyme systems capable to be activated in a wireless fashion. Conjugation of α-amylase and L-aspartate oxidase to the surface of magnetic nanoparticles and using different strategies obtaining different orientations of the enzymes respect to NP surface. This allowed us to create effective biocatalysts with different activities (ranging from 17 to 87 % of the initial activity). Furthermore, spectroscopic studies showed that the conjugation of the enzyme to the NP modifies its 3D structure and that different conjugation strategies lead to different stretching of the protein. Results clearly demonstrate that the application of an AMF activates the nano-systems, without a significant increasing in the reaction media temperature. Furthermore, we successfully reused the nano-systems for at least three consecutive cycles of AMF activation with the loss of only the 40% of the initial activity. 2) Magnetic Hyperthermia and 3D cell culture models: Understanding the mechanisms involved in the cellular damage generated by magnetic hyperthermia is crucial for its successful application. In order to evaluate the treatment efficacy, two different 3D cell culture models were prepared using a collagen matrix, which is one of the major component of the tumour extracellular matrix. A strong effect of the hyperthermia treatment was observed on the location of the particles within the 3D cell culture for one of the models. The treatment facilitated the migration of the particles from the outer areas of the 3D structure, achieving a faster homogeneous distribution throughout the whole structure and providing access to the particles to the inner cells. Moreover, although in both models cells were exposed to the same amount of nanoparticles, as a consequence of the 3D model generation, the cell death mechanism activated by the magnetic hyperthermia treatment was different in both models.

Resumen del trabajo presentado al NanoBio&Med, celebrado en Barcelona (España) del 20 al 22 de noviembre de 2018.

Peer Reviewed