RESEARCH
Our research lines are focused on the development of multifunctional composite materials for applications in biology and medicine.
We design, synthesize, and customize nano- and micro-materials with applications in therapy, diagnostics and imaging. We work at the interface of materials science, biology, and medicine with the goal of producing next generation “smart” materials, having enhanced multifunctional capabilities. We are interested in exploring radically new solutions to scientific challenges in biology and medicine, as well as in basic research in materials with interesting new properties of technological interest (energy and circular economy). See more details in the description of our research lines.
Our current research lines
Coloidal Nanoparticles (NPs)
We develop, optimize and adapt bottom-up synthetic routes for the production of NPs made of different inorganic materials, such as luminescent-type (QDs, upconverting, perovskites), metallic (Au, Ag, Cu, Pd), magnetic (iron oxides, FePt, Mn/Co/Zn Fe-substituted ferrites) as well as in nanosized MOFs (metal-organic frameworks, including the families ZIF, UiO, PCN, NU, DUT, etc.). We develop methods to adjust size, shape and coatings, which allow us to produce colloidally stable, robust NPs for a variety of bio-applications. We work on nanocomposites comprising inorganic NPs and MOFs, as well as other innovative nanohybrids composed of NPs and organic structures (liposomes, polymeric capsules, biomimetics… )
DNA-Origami Nanotechnology
We develop a state-of-the-art DNA-Origami technology to self-assemble pre-designed 3D ligand configurations with sub-nanometer precision (nanopatterning) onto colloidal nanoparticles (NPs). We aim to develop artificial NPs’ libraries with a pre-designed discrete number of ligands in any desired spatial arrangement (i.e., inspired by nature such as virus capsids), which so far has not been feasible by any method (in solution or otherwise).
In the first stage, the fabricated libraries of NPs (different size and shape) will determine the corresponding libraries of DNA-origamis having pre-designed voids (shape, size, 3D ligand “stamps”, etc.), proving the versatility and robustness of the nanoprinters.
In a second stage, as a proof of concept inspired by previous knowledge on specific receptor-mediated endocytotic pathways and virus-cell interactions, we will use the nanoprinters to fabricate a discrete number of NPs with specific ligand configurations (ligand ID, number4, density, and 3D arrangement). The trafficking behaviour of these bio-inspired NPs within cells and tissue models, will serve us to correlate their potential escape from endosome (thereby avoiding lysosomal degradation as viruses do). The proposed demonstrations will contribute to advance future developments in nanomedicine (this approach would be easily extended to any nanocarrier), and other applications in which precision is important (e.g., formation of metamaterials by NPs self-assembly).
Biomimetic Nanosystems
We seek for engineering bioinspired nanomaterials that mimic as much as possible the biological characteristics of components and structures that are part of living organisms such as viruses, bacteria or cell membranes. Naturally occurring nanostructures have key inherent class properties to develop “precision nano-therapeutics” enable of governing sophisticated bio-interface related mechanisms. Translating cell membrane features and thus, being capable of implementing their surface properties on nanomedicines, offer exciting opportunities to fabricate next generation biomimetic nanoformulations with enhanced pharmacokinetic and tissue-specific targeting capabilities. Cell membrane-derived nanostructures have proven to be the future of bioinspired synthetic nanocarriers for nanovaccines and drug-delivery systems. Nanocarriers with a surface that mimics different cellular compositions (such as leukocytes, platelets, erythrocytes, macrophages or tumoral cells) can be programmed to perform specific biological tasks such as immune escape, lymphocyte and dendritic cell activation, endothelial adhesion, and homotypic targeting.
These biomimetic nanosystems, designed by self-assembly of components derived from cells, mimic the multicompartmental architecture, complexity, and dynamism of the cellular membrane, which regulates cell-to-cell signalling and transport processes. We also engineer hybrid biomimetic nanostructures, which combine cell membrane components and organic or inorganic NPs to create functional nano bio-inorganic assemblies with physical (e.g., inorganic NPs) and biomimetic capabilities. We aim to develop a novel class of a versatile drug delivery system which selectively target cells and efficiently intracellular deliver an encapsulated cargo without compromising the safety of the organisms. Their versatile potential application for the treatment of different diseases may be achieved by selecting the specific cargo and a biomimetic coating capable of translating and implementing specific cell functions.
Nanobio interactions
A deeper and more detailed understanding of the interactions between nanomaterials and the living organisms is critical to overcome the gab that exist between bionanotechnology and the development of nanomedicines. Despite all the advances that have been achieved so far, there is still much work to be done to clarify the underlying mechanisms associated with delivery at the nanoscale and to get more reliable and translatable results.
We are interested in characterizing the interaction of “our” engineered nanomaterials with biologically relevant entities. We use and develop methods (colloidal stability, nanotoxicology, internalization, …) to assess the impact of our materials in living entities, as well as to characterize what happens to “our materials” in biologically relevant environments (cell cultures, animals, ...).We aim to understand and control of nanomaterial interactions with the surrounded biomolecules and cells, elucidating internalization pathways in more realistic three-dimensional (3D) cell culture in vitro models. The use of 3D cell cultures represents an intermediate level of complexity, and they are well suited to get a more accurate evaluation about the transport of materials than with 2D cell cultures. 3D cell cultures allow the cultured cells to resemble their original organ architecture, physiology, biomechanics, signalling and biochemistry by allowing more realistic cell interactions and connections. New 3D approaches offer a more realistic cell environment and reduce the need of performing animal studies.
Nanoparticle Immunity
We are interested in understanding the interactions between our nanosized objects and the immune system for determination of nanoparticle-driven outcomes that will influence their potential use for therapeutic applications, for example, for vaccine development. We focus on key processes triggering innate immunity (not pathogen specific) and the downstream modulation of adaptive immunity (pathogen specific). To do that, we use a range of in vitro assays to depict the interaction with relevant blood plasma proteins (e.g., Complement proteins or immunoglobulins) triggering the activation of immune cascades that derive in the activation of innate immune cells, like dendritic cells (DCs) and macrophages, and the internalization of nanomaterials. We aim to correlate the biomolecular surfaces of nanomaterials with specific recognition by innate Pattern Recognition Receptors (PRRs) expressed in different murine and human immune cell line models (Raw264.7, JawsII, THP-1 and MUTZ-3). We can gain a basic understanding of NP internalization, fate, and immunogenicity, and use such information to design functional materials. Currently, we are developing a range of “smart” biomimetic nanoparticles like cell-membrane based vesicles and functional DNA-origamis, that can be precisely loaded and modified with immunomodulating agents, for exerting precise effects on innate and adaptive immunity ex vivo, using human blood donor samples. We study the differential uptake by specific innate cell subsets (e.g., macrophages, conventional DCs or monocytic DCs), the induced functional profile in those cells, and their capabilities to modulate adaptive responses mediated by the donor’s T lymphocytes. By doing so, we can connect the differential features of the NPs, for example, immunogenic ligand density, orientation and loaded cargoes, to the outcome response. We apply mainly multicolor flow cytometry and proteomics for such tasks, obtaining a detailed landscape of the features driving immunity.
