(Alphabetical order - Team leader)
Our research is focused on the interaction of metal ions and metallic compounds with biomolecules (proteins, DNA, etc.) and of biomolecules between them (like the metallothionein/ferritin or metallothionein/hemocyanin couples), using different techniques, i.e. UV-vis absorption, circular dichroism, fluorescence, and mass spectrometry (ESI-MS, ICP-MS). Additionally, the evaluation of the cytotoxicity of metallic compounds and the mechanism of cellular death, as well as the cellular uptake and distribution of the metals, are also normal studies carried out in our group. We are also designing and preparing metal complexes (Pt, Ru and Cu) with putative anticancer activity, the main characteristic of which lays on the use of photosensitive ligands based on azobenzenes, able to modulate the reactivity of the metallic moiety simply by controlled irradiation.
Another research line is devoted to the preparation of target specific Tc-99m radiopharmaceuticals by functionalization of biomolecules. The homologous rhenium complexes are studied as structural models of technetium compounds and, in addition, this information is useful to the development of therapeutical Re-188 radiopharmaceuticals, according to the theranostic pair Tc-99m/Re-188.
Finally, we are developing “metalloliposomes”, which are supramolecular structures with arrangements very similar to those of liposomes but they contain metallic groups in the bilayer structure. Currently, we are working with metallosomes that can act as CO releasing molecules but we plan to use the same strategy for other therapeutical uses.
The BionaMet team develops bioplatforms as biocarriers of optically and magnetically active nanoparticles for imaging and therapy. These bioplatforms are based on
proteins and living probiotic bacteria, which specifically accumulate in the liver and bowel, respectively. Molecule-based drugs can also be incorporated into the nanostructures (bioplatform +
nanoparticles), thus obtaining targeted multifunctional nanoprobes for theranotics.
We use TEM techniques for characterize the nanostructures, including HAADF, EDX, EELS and HREM modes.
Current research is focused on the exploitation of the variety and richness of coordination chemistry (allowing unlimited combinations between organic ligands and metal ions) to tackle two important health issues, i.e. cancer and Alzheimer's disease (AD).
● In cancer research, our investigation deals with
- the design and preparation of small, highly cytotoxic metal-based molecules and their nanoencapsulation in nano-objects that can be functionalized (drug delivery and targeting);
- the development of novel metallodrugs in a structure-targeted approach to interact with DNA supramolecules, e.g. three-way junctions or G-quadruplexes (cancer-cell-selective agents);
- the generation of photoswitchable metal complexes based on the photo-modification of the ligands (an unprecedented approach in photoactivated chemotherapy ‒ PACT ‒, which is currently metal centred).
● In AD research, our innovative approach consists in designing and preparing selective (fluorescent) peptide-based copper chelators and conjugating them to emissive nanoparticles (quantum dots, gold nanoparticles, etc...). Such peptide-decorated nanoparticles allow the detection of copper and its brain location (fluorescent probe), and the re-establishment of normal metallo-trafficiking, therefore reducing oxidative stress (Metal Protein Attenuating Compound); these nanocompounds therefore act as AD theranostic (therapy + diagnosis) agents.
Team Leaser: Javier García Tojal; mail
Team members: Gustavo Adolfo Espino Ordóñez, Aránzazu Mendía Jalón, María Remedios Pedrosa Sáez
Region: Castile and León
The research group at the University of Burgos works on the synthesis of new coordination compounds and the study of structure-property and structure-activity relationships. The chemical systems studied are diverse: palladium- and platinum-thionate derivatives, organometallic complexes of ruthenium(II), rhodium(III) and iridium(III), molybdenum complexes, first-row transition metal ions with polydentate ligands (e.g. thiosemicarbazonecopper(II) compounds) and d-f metal systems with dinucleating ligands. We analyse the interaction of these metal-based compounds with biomolecules such as nucleobases, and we investigate their spectroscopic and magnetic features, their catalytic activity and antitumoral properties. Our goals are to find structural and functional models of biological systems involving metal ions related with human diseases and to achieve compounds with potential applications in the fields of chemotherapy and bioimaging.
Our research interests focus on the design of luminescent and bioactive novel metallic complexes in order to develop new biological sensors and biomarkers, as well as the next generation of metallodrugs. The research is mainly divided in the following working lines:
1) Development of biologically active metallic species, mainly with group 11 metal complexes and using different types of ligands.
2) Design of gold-based peptidomimetics for selective drug delivery at tumor target sites.
3) Development of light-emissive complexes for bioimaging applications.
4) Design of theranostic metallic agents, including d6, d8 and d10 metal complexes and lanthanides complexes.
5) Bioactive silver and gold nanoparticles.
Our groups carries out the evaluation of the cytotoxic, antibacterial or anti-VIH activity of metallic compounds, together with the study of the mechanism of cellular death and cellular uptake and biodistribution.
Our research is focused on the development of non-conventional anticancer metallodrugs, mainly using platinum as metal, and the study of their mechanism of action. We aimed at targeting selectively tumours by identifying specific interactions with biomolecules, besides DNA. The metal complexes are rationally designed by modifying the chemical structures of known active platinum complexes, exploiting the biological properties of the ligands, using different leaving groups and oxidation states of the metal ions. The main goal is to obtain platinum drugs with enhanced activities, and load them onto carriers (drug delivery). Furthermore, the study of the interaction of these complexes with different biomolecules (applying biophysical methods) allows assessing their specific mode of action, which is crucial for the design of improved metallodrugs. Novel drug-activation approaches are also employed, e.g. photoactivation of the metallodrugs.
Research is focused on the generation of metal complexes as both imaging agents and therapeutics. The team is interested in DNA recognition and metal-based anticancer drugs. Supramolecular chemistry is applied to construct large synthetic assemblies that can recognize DNA structures (major or minor groove, three-way junctions and so on). Furthermore, molecular design is also used to encode the precise micro-architecture, and to explore routes to encode additional information into the array, such as strand directionality, groove size and chirality. Hence, fluorescent anticancer metallodrugs are prepared with metal ions like Au(I), Ag(I) and Pt(II), and their uptake and localization are investigated by fluorescence microscopy. These compounds can be used as imaging tools to directly investigate relevant interactions between metallodrugs and different biomolecules. Combining supramolecular design with cisplatin-type design is also a topic of interest of this group, with the ultimate objective to achieve more efficient drugs.
Team Leader: José Ruiz López; mail
Team members: Venancio Rodríguez Hernández, María Dolores Santana Lario, Natalia Cutillas Aulló, Consuelo Vicente López, Concha de Haro García
PhD students: Gloria Vigueras Bautista, Francisco José Ballester Hernández, Enrique Ortega Forte
Our investigation deals with:
1) The design and preparation of noble-metal anticancer drugs and antiangiogenic agents based on the benzimidazole pharmacophore and benzylamine, including new fluorescent coordination compounds.
2) The targeted transport of the most active drugs by conjugation to small peptides, other biomolecules or DNA intercalators.
3) The preparation of noble-metal-based drugs loaded on silk-fibroin nanoparticles to improve cell internalization and to overcome resistance mechanisms.
4) Targeting drug delivery using magnetic nanoparticles.
Finally, we are developing new inhibitors of amyloid-b aggregation based on iridium(III) complexes.