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Acuerdo transformativo, Despite the large number of synthesis methodologies described for superparamagnetic iron oxide nanoparticles (SPIONs), the search for their large-scale production for their widespread use in biomedical applications remains a mayor challenge. Flame Spray Pyrolysis (FSP) could be the solution to solve this limitation, since it allows the fabrication of metal oxide nanoparticles with high production yield and low manufacture costs. However, to our knowledge, to date such fabrication method has not been upgraded for biomedical purposes. Herein, SPIONs, European Union, Ministerio de Ciencia e Innovacion de España, Depto. de Química en Ciencias Farmacéuticas, Fac. de Farmacia, TRUE, pub

RESEARCHER ID M-3378-2014 (María Vallet Regí) ORCID 0000-0002-6104-4889 (María Vallet Regí) RESEARCHER ID K-4773-2015 (Blanca González Ortiz) ORCID 0000-0002-0493-6071 (Blanca González Ortiz), One of the main problems with drug-based cancer treatments is the lack of selectivity, which causes them to be distributed non-specifically in the body and cells, generating undesirable side effects. In this work, a novel hybrid nanosystem for cancer cell targeting and therapeutic delivery of Ag nanoparticles has been designed. The proposed nanosystem contains a Ag core coated with a mesoporous silica shell which prevents the aggregation of Ag nanoparticles and allows the anchoring of transferrin as a targeting ligand, thus enabling the nanosystem to be selectively directed to cancer cells that overexpress transferrin receptors. The analytical and functional characterization of the nanosystem has allowed to demonstrate selective internalization and its cytotoxic potential in cancer cells where it induces apoptosis. Additional bioanalytical experiments have enabled the identification of different transcripts and altered proteins in cells treated with the nanosystem, which has made it possible to delve deeper into the biomolecular mechanisms by which the nanosystem exerts its action. Furthermore, a hemocompatibility study indicates neither activation of monocytes nor platelet aggregation after nanosystem exposure, hence supporting the future clinical applicability of the Ag@MSNs-Tf nanosystem., Unión Europea. Horizonte 2020, Ministerio de Economía y Competitividad (MINECO), Instituto de Salud Carlos III, Depto. de Química Analítica, Depto. de Química en Ciencias Farmacéuticas, Fac. de Ciencias Químicas, Fac. de Farmacia, TRUE, pub

RESEARCHER ID M-9921-2014 (Isabel Izquierdo Barba) ORCID 0000-0002-4139-4646 (Isabel Izquierdo Barba) RESEARCHER ID K-8193-2014 (Alejandro Baeza) ORCID 0000-0002-2026-6266 (Alejandro Baeza) RESEARCHER ID M-3378-2014 (María Vallet Regí) ORCID 0000-0002-6104-4889 (María Vallet Regí), One of the major concerns in the application of nanocarriers in oncology is their scarce penetration capacity in tumoral tissues, which drastically compromises the effectivity. Living organisms as cells and bacteria present the capacity to navigate autonomously following chemical gradients being able to penetrate deeply into dense tissues. In the recent years, the possibility to employ these organisms for the transportation of therapeutic agents and nanocarriers attached on their membrane or engulfed in their inner space have received huge attention. Herein, based on this principle, a new approach to deliver drug loaded nanoparticles achieving high penetration in tumoral matrices is presented. In this case, Escherichia coli (E. coli) bacteria wall is decorated with azide groups, whereas alkyne-strained groups are incorporated on the surface of mesoporous silica nanoparticles loaded with a potent cytotoxic compound, doxorubicin. Both functional groups form stable triazole bonds by click-type reaction allowing the covalent grafting of nanoparticles on living bacteria. Thus, the motility and penetration capacity of bacteria, which carried nanoparticles are evaluated in a 3D tumoral matrix model composed by a dense collagen extracellular matrix with HT1080 human fibrosarcome cells embedded. The results confirmed that bacteria are able to transport the nanoparticles crossing a thick collagen layer being able to destroy almost 80% of the tumoral cells located underneath. These findings envision a powerful strategy in nanomedicine applied for cancer treatment by Q4 allowing a homogeneous distribution of therapeutic agents in the malignancy., Unión Europea. Horizonte 2020, Depto. de Química en Ciencias Farmacéuticas, Fac. de Farmacia, TRUE, inpress

Machine learning-inspired approaches allow for processing of multidimensional data and have shown to uncover clinical patterns in several human diseases. Recently it has been used to model cGVHD risk groups according to clinical data, but the role of this approach applied to gene-expression-profile (GEP) data has not been established yet. In this study, we aimed to unravel specific GEP patterns associated to cGVHD using machine-learning analyses. For this purpose, we isolated peripheral blood T-lymphocytes drawn from normal healthy donors and from patients who had underwent allogeneic hematopoietic stem cell transplantation (allo-HSCT) with and without cGVHD symptoms. Dataset obtained in HG-U133 Plus 2.0 Gene Chip oligonucleotide array were wrapped by Boruta method based on Random Forest. Thus, a limited set of 53 genes was retained and two-dimensional Principal Component Analysis plots projection was plotted showing a clear distinction of cGVHD with No-cGVHD and healthy Control groups with area under the curve (AUC) over 0.75 for each comparison. The highest scored genes were CDKN2A, SERPINB9, LYPLA1 y CKTM1A/B genes which are involved in positive regulation of cellular senescense with protection against perforin-dependent apoptosis. Altogether our novel findings, using machine-learning approach applied to GEP in cGVHD unravel a limited panel of five genes with a potential diagnostic and targeted therapy.