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Quadruplex structures have been identified in a plethora of organisms where they play important functions in the regulation of molecular processes, and hence have been proposed as therapeutic targets for many diseases. In this paper we report the extensive bioinformatic analysis of the SARS-CoV-2 genome and related viruses using an upgraded version of the open-source algorithm G4-iM Grinder. This version improves the functionality of the software, including an easy way to determine the potential biological features affected by the candidates found. The quadruplex definitions of the algorithm were optimized for SARS-CoV-2. Using a lax quadruplex definition ruleset, which accepts amongst other parameters two residue G- and C-tracks, 512 potential quadruplex candidates were discovered. These sequences were evaluated by their in vitro formation probability, their position in the viral RNA, their uniqueness and their conservation rates (calculated in over seventeen thousand different COVID-19 clinical cases and sequenced at different times and locations during the ongoing pandemic). These results were then compared subsequently to other Coronaviridae members, other Group IV (+)ssRNA viruses and the entire viral realm. Sequences found in common with other viral species were further analyzed and characterized. Sequences with high scores unique to the SARS-CoV-2 were studied to investigate the variations amongst similar species. Quadruplex formation of the best candidates were then confirmed experimentally. Using NMR and CD spectroscopy, we found several highly stable RNA quadruplexes that may be suitable therapeutic targets for the SARS-CoV-2.

A modified diamond–photonics based metrology is proposed to explore the magnetic fields created by agglomerates of magnetic nanoparticles (MNPs). MNPs are promising for environmental and medical applications; those proposed for cancer magnetic hyperthermia treatments are small superparamagnetic <20 nm iron oxide particles. Inside cells, they assemble in larger MNP agglomerates, reaching cross-sections of several micrometers. Here, these conditions are reproduced and MNP agglomerates immobilized. Optically detected magnetic resonance (ODMR) signals recorded without a bias field in a confocal microscope and scanning across a homogenous shallow layer of fluorescent nitrogen-vacancy centers in a bulk diamond sample placed in direct contact with the MNP agglomerates are used to determine magnetic fields with a spatial resolution of 500 nm in a lateral direction. This spatial resolution allows determining magnetic field maps around individual MNP agglomerates, for which magnetic fields with strengths ranging from 0.03 mT to maximal 1.2 mT in the direct vicinity of the agglomerates and with detectable fields up to 5 µm away from the agglomerates, are determined. Based on the findings, a pathway to non-invasively study the micro/nano topology of MNP agglomerates is proposed.

Implantable long-acting delivery systems able to minimize off-target side effects and locally provide non-invasive imaging reporting are of utmost importance to offer a precise treatment of internal diseases and accurate assessment of disease progression, such as in local infections and tumor relapse following surgery, among other diseases. Here, a biocompatible xanthan gum/Fe3O4-based drug-loaded magnetic nanoparticle composite hydrogel with suitable rheological properties and theranostic performance was designed. The ultra-high efficacy of the chemically modified polysaccharide matrix to simultaneously encapsulate hydrophilic drugs and magnetic iron oxide nanoparticles rendered the final hydrogel magnetically responsive to enable thermally induced controlled drug delivery by magnetic hyperthermia as well as non-invasive monitoring by magnetic resonance imaging (MRI). In addition to an enhanced activity of the drug-loaded hydrogel compared to the free drug, results showed that the application of an alternating magnetic field efficiently stimulated a 3-fold faster release of the encapsulated drug compared to passive conditions, whereas a concentration-dependent shortening of the water protons’ relaxation time at a clinical field of 3 T confirmed this magnetic hydrogel as a T2-MRI contrast enhancer. Altogether, these properties open a novel dimension for the application of these versatile magnetic nanoparticle composite hydrogels, from traditional topical uses to more internal surgery interventions in dentistry, oncology, or wound healing of critical skin damage and infections.

In this paper we report the analysis of the 2019-nCoV genome and related viruses using an upgraded version of the open-source algorithm G4-iM Grinder. This version improves the functionality of the software, including an easy way to determine the potential biological features affected by the candidates found. The quadruplex definitions of the algorithm were optimized for 2019-nCoV. Using a lax quadruplex definition ruleset, which accepts amongst other parameters two residue G- and C-tracks, hundreds of potential quadruplex candidates were discovered. These sequences were evaluated by their in vitro formation probability, their position in the viral RNA, their uniqueness and their conservation rates (calculated in over three thousand different COVID-19 clinical cases and sequenced at different times and locations during the ongoing pandemic). These results were compared sequentially to other Coronaviridae members, other Group IV (+)ssRNA viruses and the entire realm. Sequences found in common with other species were further analyzed and characterized. Sequences with high scores unique to the 2019-nCoV were studied to investigate the variations amongst similar species. Quadruplex formation of the best candidates was then confirmed experimentally. Using NMR and CD spectroscopy, we found several highly stable RNA quadruplexes that may be suitable theranostic targets against the 2019-nCoV.

Nanomedicine is a new field employing nanotechnology tools for biomedical applications. Nanomaterials feature sizes between 1 and 100 hundred nanometers, and therefore they fill the gap between single molecules and bulk materials. They open the possibility to access biological processes on the same size scale. Nanoparticles have shown great potential to achieve the goal of personalized medicine due to the possibilities to modify their surface with proteins, targeting molecules, or imaging probes. Particularly, iron oxide nanoparticles show promising properties for successful application in biomedicine due to their low-cost production, high biocompatibility, and great magnetic response. Strategies for the functionalization of inorganic cores have been developed over the past years, and efforts have been devoted to engineering nanoparticles with multifunctional ligands on the surface to enable active tumor targeting, detection over different imaging modalities, and stimulus-driven cargo release. During this Ph.D. thesis, three main aspects of iron oxide nanoparticles have been evaluated. First, the stability of nanoparticles has been addressed in biological fluids. Second, the uptake of nanoparticles by stem cells for cell tracking applications was studied with nanoparticles of different sizes and bearing different organic coatings. Third, new possibilities of chemical functionalization of naked iron oxide nanoparticles by orthogonal processes have been explored, in order to achieve high yields, simplicity and high reproducibility.

A colloidally stable dispersion of anisotropic Ni nanowires in water has been achieved showing good performance as a T-contrast agent in magnetic resonance imaging (MRI). A wet chemistry approach has been developed that renders water dispersible Ni nanowires of controlled size. Firstly, an array of Ni/Au multilayer nanowires of tailored dimensions was synthesized by pulsed electrodeposition within a porous alumina template in a three-electrode cell at room-temperature. Then, Ni/Au multilayer nanowires were released from the template followed by the isolation of the Ni segments through a two-step acidic etching, ending up with a colloidally stable dispersion of poly-acrylic acid (PAA)-coated Ni nanowires in water solution. The PAA-coated Ni nanowires have been morphologically and structurally characterized by scanning and transmission electron microscopy (SEM, TEM, respectively), whereas their ferromagnetic properties were studied using a SQUID-magnetometer. Importantly, relaxivity properties (transversal relaxivity, r) indicated good performance of PAA-coated Ni nanowires as a T-contrast agent at 1.41 T and body temperature, with values as large as those of commercial contrast agents based on iron oxide nanoparticles. MRI phantom imaging at clinical fields of 3 T confirmed the dark contrast effect of PAA-coated Ni nanowires, as compared to a water control, which opens a new window of opportunities for anisotropic metal nanostructures as contrast agents in MRI applications.

In the last years, NaxCoO2 has experienced a renewed interest in the field of solid state science. However, NaxCoO2 is not a novel material, it has been extensively studied for decades. In the 80´s, it was investigated due to its electrochemical properties (high ionic mobility, high electrical conduction) and tested as a cathod in reversible alkaline cells, as its analogous LixCoO2. In the 90’s, its thermoelectric properties raised the interest of this material for energy harvesting at high temperature and refrigeration. However, the discovery of novel properties (i.e. high thermoelectric power or, mainly, the occurrence of superconductivity below 5K) and their possible relationship with similar phenomena found in other materials boosted a renewed interest in this highly electronic correlated system. The structural, magnetic and electronic properties of NaxCoO2 have been studied in detail in order to understand deeply some of the most fundamental aspects which drive the chemical and physical behaviour of this system: presence of oxygen vacants, the role of water played in the occurrence of superconductivity, the proximity of the system to a quantum phase transition or the nature of the unconventional thermoelectric and magnetic properties with x, specifically at the half-doped x=0.5. All of them are kept under strong scientific discussions that, far from solving them, contribute to generate an even higher controversy. On other hand, the efficiency of topotactic reactions in order to exchange Na+ ions by other mono- or di-valent ions, such as Li+, Ca2+ or Sr2+, has been studied. The physical properties of the resulting compounds are shown and compared to those ones from the analogous NaxCoO2 precursor. Therefore, in the pages inside, the reader will can find our main results and conclusions achieved in each one of these subjects, in a modest attempt to explain the chemistry and physics involved in NaxCoO2 and related compounds.