Browsing by MeSH term "Nanoparticles"
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Publication BET inhibitor nanotherapy halts kidney damage and reduces chronic kidney disease progression after ischemia-reperfusion injury.(Elsevier, 2024-05) Saiz, Maria Laura; Lozano-Chamizo, Laura; Florez, Aida Bernardo; Marciello, Marzia; Diaz-Bulnes, Paula; Corte-Iglesias, Viviana; Bernet, Cristian Ruiz; Rodrigues-Diez, Raul R; Martin-Martin, Cristina; Rodriguez-Santamaria, Mar; Fernandez-Vega, Ivan; Rodriguez, Ramon M; Diaz-Corte, Carmen; Suarez-Alvarez, Beatriz; Filice, Marco; Lopez-Larrea, Carlos; Instituto de Salud Carlos III; Unión Europea. Comisión Europea. NextGenerationEU; Sociedad Española de Nefrología; Gobierno del Principado de Asturias (España); Comunidad de Madrid (España)Targeting epigenetic mechanisms has emerged as a potential therapeutic approach for the treatment of kidney diseases. Specifically, inhibiting the bromodomain and extra-terminal (BET) domain proteins using the small molecule inhibitor JQ1 has shown promise in preclinical models of acute kidney injury (AKI) and chronic kidney disease (CKD). However, its clinical translation faces challenges due to issues with poor pharmacokinetics and side effects. Here, we developed engineered liposomes loaded with JQ1 with the aim of enhancing kidney drug delivery and reducing the required minimum effective dose by leveraging cargo protection. These liposomes efficiently encapsulated JQ1 in both the membrane and core, demonstrating superior therapeutic efficacy compared to freely delivered JQ1 in a mouse model of kidney ischemia-reperfusion injury. JQ1-loaded liposomes (JQ1-NPs) effectively targeted the kidneys and only one administration, one-hour after injury, was enough to decrease the immune cell (neutrophils and monocytes) infiltration to the kidney-an early and pivotal step to prevent damage progression. By inhibiting BRD4, JQ1-NPs suppress the transcription of pro-inflammatory genes, such as cytokines (il-6) and chemokines (ccl2, ccl5). This success not only improved early the kidney function, as evidenced by decreased serum levels of BUN and creatinine in JQ1-NPs-treated mice, along with reduced tissue expression of the damage marker, NGAL, but also halted the production of extracellular matrix proteins (Fsp-1, Fn-1, α-SMA and Col1a1) and the fibrosis development. In summary, this work presents a promising nanotherapeutic strategy for AKI treatment and its progression and provides new insights into renal drug delivery.Publication Biological Implications of a Stroke Therapy Based in Neuroglobin Hyaluronate Nanoparticles. Neuroprotective Role and Molecular Bases.(2021-12-27) Peinado, María Ángeles; Ovelleiro, David; Del Moral, María Luisa; Hernández, Raquel; Martínez-Lara, Esther; Siles, Eva; Pedrajas, José Rafael; García-Martín, María Luisa; Caro, Carlos; Peralta, Sebastián; Morales, María Encarnación; Ruiz, María Adolfina; Blanco, SantosExogenous neuroprotective protein neuroglobin (Ngb) cannot cross the blood-brain barrier. To overcome this difficulty, we synthesized hyaluronate nanoparticles (NPs), able to deliver Ngb into the brain in an animal model of stroke (MCAO). These NPs effectively reached neurons, and were microscopically identified after 24 h of reperfusion. Compared to MCAO non-treated animals, those treated with Ngb-NPs showed survival rates up to 50% higher, and better neurological scores. Tissue damage improved with the treatment, but no changes in the infarct volume or in the oxidative/nitrosative values were detected. A proteomics approach (p-valuePublication Biophysical properties of single rotavirus particles account for the functions of protein shells in a multilayered virus(eLife Sciences Publications, 2018) Jiménez-Zaragoza, Manuel; Yubero, Marina Pl; Martin-Forero, Esther; Castón, Jose R; Reguera, David; Luque, Daniel; de Pablo, Pedro J; Rodriguez Martinez, Javier M; Ministerio de Economía y Competitividad (España); Comunidad de Madrid (España)The functions performed by the concentric shells of multilayered dsRNA viruses require specific protein interactions that can be directly explored through their mechanical properties. We studied the stiffness, breaking force, critical strain and mechanical fatigue of individual Triple, Double and Single layered rotavirus (RV) particles. Our results, in combination with Finite Element simulations, demonstrate that the mechanics of the external layer provides the resistance needed to counteract the stringent conditions of extracellular media. Our experiments, in combination with electrostatic analyses, reveal a strong interaction between the two outer layers and how it is suppressed by the removal of calcium ions, a key step for transcription initiation. The intermediate layer presents weak hydrophobic interactions with the inner layer that allow the assembly and favor the conformational dynamics needed for transcription. Our work shows how the biophysical properties of the three shells are finely tuned to produce an infective RV virion.Publication Dual bioresponsive antibiotic and quorum sensing inhibitor combination nanoparticles for treatment of Pseudomonas aeruginosa biofilms in vitro and ex vivo(Royal Society of Chemistry (RSC), 2019-10-01) Singh, Nishant; Romero, Manuel; Travanut, Alessandra; Monteiro, Patricia F; Jordana-Lluch, Elena; Hardie, Kim R; Williams, Paul; Alexander, Morgan R; Alexander, CameronMany debilitating infections result from persistent microbial biofilms that do not respond to conventional antibiotic regimens. A potential method to treat such chronic infections is to combine agents which interfere with bacterial biofilm development together with an antibiotic in a single formulation. Here, we explore the use of a new bioresponsive polymer formulation derived from specifically modified alginate nanoparticles (NPs) in order to deliver ciprofloxacin (CIP) in combination with the quorum sensing inhibitor (QSI) 3-amino-7-chloro-2-nonylquinazolin-4(3H)-one (ACNQ) to mature Pseudomonas aeruginosa biofilms. The alginate NPs were engineered to incorporate a pH-responsive linker between the polysaccharide backbone and the QSI, and to encapsulate CIP via charge-charge interactions of the positively-charged drug with the carboxyl residues of the alginate matrix. In this way, a dual-action release of antibiotic and QSI was designed for the low-pH regions of a biofilm, involving cleavage of the QSI-linker to the alginate matrix and reduced charge-charge interactions between CIP and the polysaccharide as the alginate carboxyl side-chains protonated. When tested in a biofilm model the concomitant release of CIP + QSI from the pH-responsive nanoparticles significantly reduced the viability of the biofilm compared with CIP treatment alone. In addition, the alginate NPs were shown to penetrate deeply into P. aeruginosa biofilms, which we attribute in part to the charges of the NPs and the release of the QSI agent. Finally, we tested the formulation in both a 2D keratinocyte and a 3D ex vivo skin infection model. The dual-action bio-responsive QSI and CIP release nanoparticles effectively cleared the infection in the latter, suggesting considerable promise for combination therapeutics which prevent biofilm formation as well as effectively killing mature P. aeruginosa biofilms.Publication Dual-labeled nanoparticles based on small extracellular vesicles for tumor detection.(BioMed Central (BMC), 2022-11-14) Santos-Coquillat, Ana; Herreros-Pérez, Desiré; Samaniego, Rafael; González, María Isabel; Cussó, Lorena; Desco, Manuel; Salinas, Beatriz; Ministerio de Ciencia e Innovación (España); Instituto de Salud Carlos III; Comunidad de Madrid (España); Unión Europea. Fondo Europeo de Desarrollo Regional (FEDER/ERDF); Agencia Estatal de Investigación (España); Unión Europea. Fondo Social Europeo (ESF/FSE); Fundación BBVA; Fundación Ramón Areces; Instituto de Investigación Sanitaria Gregorio MarañónSmall extracellular vesicles (sEVs) are emerging natural nanoplatforms in cancer diagnosis and therapy, through the incorporation of signal components or drugs in their structure. However, for their translation into the clinical field, there is still a lack of tools that enable a deeper understanding of their in vivo pharmacokinetics or their interactions with the cells of the tumor microenvironment. In this study, we have designed a dual-sEV probe based on radioactive and fluorescent labeling of goat milk sEVs. The imaging nanoprobe was tested in vitro and in vivo in a model of glioblastoma. In vitro assessment of the uptake of the dual probe in different cell populations (RAW 264.7, U87, and HeLa) by optical and nuclear techniques (gamma counter, confocal imaging, and flow cytometry) revealed the highest uptake in inflammatory cells (RAW 264.7), followed by glioblastoma U87 cells. In vivo evaluation of the pharmacokinetic properties of nanoparticles confirmed a blood circulation time of ~ 8 h and primarily hepatobiliary elimination. The diagnostic capability of the dual nanoprobe was confirmed in vivo in a glioblastoma xenograft model, which showed intense in vivo uptake of the SEV-based probe in tumor tissue. Histological assessment by confocal imaging enabled quantification of tumor populations and confirmed uptake in tumor cells and tumor-associated macrophages, followed by cancer-associated fibroblasts and endothelial cells. We have developed a chemical approach for dual radioactive and fluorescent labeling of sEVs. This methodology enables in vivo and in vitro study of these vesicles after exogenous administration. The dual nanoprobe would be a promising technology for cancer diagnosis and a powerful tool for studying the biological behavior of these nanosystems for use in drug delivery.Publication Fluorescence-Based Nanoparticle Tracking Analysis and Flow Cytometry for Characterization of Endothelial Extracellular Vesicle Release.(Multidisciplinary Digital Publishing Institute (MDPI), 2020-12-04) Oesterreicher, Johannes; Pultar, Marianne; Schneider, Jaana; Mühleder, Severin; Zipperle, Johannes; Grillari, Johannes; Holnthoner, Wolfgang; Austrian Research Promotion Agency; FWF Austrian Science Fund; Particle MetrixAs extracellular vesicles (EVs) have become a prominent topic in life sciences, a growing number of studies are published on a regular basis addressing their biological relevance and possible applications. Nevertheless, the fundamental question of the true vesicular nature as well as possible influences on the EV secretion behavior have often been not adequately addressed. Furthermore, research regarding endothelial cell-derived EVs (EndoEVs) often focused on the large vesicular fractions comprising of microvesicles (MV) and apoptotic bodies. In this study we aimed to further extend the current knowledge of the influence of pre-isolation conditions, such as cell density and conditioning time, on EndoEV release from human umbilical vein endothelial cells (HUVECs). We combined fluorescence nanoparticle tracking analysis (NTA) and the established fluorescence-triggered flow cytometry (FT-FC) protocol to allow vesicle-specific detection and characterization of size and surface markers. We found significant effects of cell density and conditioning time on both abundance and size distribution of EndoEVs. Additionally, we present detailed information regarding the surface marker display on EVs from different fractions and size ranges. Our data provide crucial relevance for future projects aiming to elucidate EV secretion behavior of endothelial cells. Moreover, we show that the influence of different conditioning parameters on the nature of EndoEVs has to be considered.Publication Identification of distinct nanoparticles and subsets of extracellular vesicles by asymmetric flow field-flow fractionation.(Nature Publishing Group, 2018-03) Zhang, Haiying; Freitas, Daniela; Kim, Han Sang; Fabijanic, Kristina; Li, Zhong; Chen, Haiyan; Mark, Milica Tesic; Molina, Henrik; Martin, Alberto Benito; Bojmar, Linda; Fang, Justin; Rampersaud, Sham; Hoshino, Ayuko; Matei, Irina; Kenific, Candia M; Nakajima, Miho; Mutvei, Anders Peter; Sansone, Pasquale; Buehring, Weston; Wang, Huajuan; Jimenez, Juan Pablo; Cohen-Gould, Leona; Paknejad, Navid; Brendel, Matthew; Manova-Todorova, Katia; Magalhães, Ana; Ferreira, José Alexandre; Osório, Hugo; Silva, André M; Massey, Ashish; Cubillos-Ruiz, Juan R; Galletti, Giuseppe; Giannakakou, Paraskevi; Cuervo, Ana Maria; Blenis, John; Schwartz, Robert; Brady, Mary Sue; Peinado, Héctor; Bromberg, Jacqueline; Matsui, Hiroshi; Reis, Celso A; Lyden, DavidThe heterogeneity of exosomal populations has hindered our understanding of their biogenesis, molecular composition, biodistribution and functions. By employing asymmetric flow field-flow fractionation (AF4), we identified two exosome subpopulations (large exosome vesicles, Exo-L, 90-120 nm; small exosome vesicles, Exo-S, 60-80 nm) and discovered an abundant population of non-membranous nanoparticles termed 'exomeres' (~35 nm). Exomere proteomic profiling revealed an enrichment in metabolic enzymes and hypoxia, microtubule and coagulation proteins as well as specific pathways, such as glycolysis and mTOR signalling. Exo-S and Exo-L contained proteins involved in endosomal function and secretion pathways, and mitotic spindle and IL-2/STAT5 signalling pathways, respectively. Exo-S, Exo-L and exomeres each had unique N-glycosylation, protein, lipid, DNA and RNA profiles and biophysical properties. These three nanoparticle subsets demonstrated diverse organ biodistribution patterns, suggesting distinct biological functions. This study demonstrates that AF4 can serve as an improved analytical tool for isolating extracellular vesicles and addressing the complexities of heterogeneous nanoparticle subpopulations.Publication Iron Oxide Nanoradiomaterials: Combining Nanoscale Properties with Radioisotopes for Enhanced Molecular Imaging(Hindawi, 2017) Pellico, Juan; Llop, Jordi; Fernandez-Barahona, Irene; Bhavesh, Riju; Ruiz-Cabello, Jesus; Herranz, Fernando; Ministerio de Economía y Competitividad (España); Instituto de Salud Carlos III; Ministerio de Economía, Industria y Competitividad (España)The combination of the size-dependent properties of nanomaterials with radioisotopes is emerging as a novel tool for molecular imaging. There are numerous examples already showing how the controlled synthesis of nanoparticles and the incorporation of a radioisotope in the nanostructure offer new features beyond the simple addition of different components. Among the different nanomaterials, iron oxide-based nanoparticles are the most used in imaging because of their versatility. In this review, we will study the different radioisotopes for biomedical imaging, how to incorporate them within the nanoparticles, and what applications they can be used for. Our focus is directed towards what is new in this field, what the nanoparticles can offer to the field of nuclear imaging, and the radioisotopes hybridized with nanomaterials for use in molecular imaging.Publication Mesoporous Silica Nanoparticles for Co-Delivery of Drugs and Nucleic Acids in Oncology: A Review(Multidisciplinary Digital Publishing Institute (MDPI), 2020-06-08) Paris, Juan L.; Vallet-Regí, María; [Paris,JL] Allergy Research Group, Instituto de Investigación Biomédica de Málaga-IBIMA, Hospital Civil, Málaga, Spain. [Paris,JL] Nanostructures for Diagnosing and Treatment of Allergic Diseases Laboratory, Andalusian Center for Nanomedicine and Biotechnology-BIONAND, Málaga, Spain. [Vallet-Regí,M] Departamento de Química en Ciencias Farmacéuticas (Unidad Docente de Química Inorgánica y Bioinorgánica), Facultad de Farmacia, Universidad Complutense de Madrid, Instituto de Investigación Sanitaria Hospital 12 de Octubre (imas12), Madrid, Spain. [Vallet-Regí,M] Centro de Investigación Biomédicaen Red de Bioingeniería, Biomateriales y Nanomedicina (CIBER-BBN), Spain.Mesoporous silica nanoparticles have attracted much attention in recent years as drug and gene delivery systems for biomedical applications. Among their most beneficial features for biomedicine, we can highlight their biocompatibility and their outstanding textural properties, which provide a great loading capacity for many types of cargos. In the context of cancer nanomedicine, combination therapy and gene transfection/silencing have recently been highlighted as two of its most promising fields. In this review, we aim to provide an overview of the different small molecule drug-nucleic acid co-delivery combinations that have been developed using mesoporous silica nanoparticles as carriers. By carefully selecting the chemotherapeutic drug and nucleic acid cargos to be co-delivered by mesoporous silica nanoparticles, different therapeutic goals can be achieved by overcoming resistance mechanisms, combining different cytotoxic mechanisms, or providing an additional antiangiogenic effect. The examples here presented highlight the great promise of this type of strategies for the development of future therapeutics.Publication Molecular effects of polystyrene nanoplastics on human neural stem cells(Public Library of Science (PLOS), 2024) Martin-Folgar, Raquel; González-Caballero, MCarmen; Torres-Ruiz, Mónica; Cañas Portilla, Ana Isabel; De Alba-González, Mercedes; Liste-Noya, Isabel; Morales, MónicaNanoplastics (NPs) have been found in many ecological environments (aquatic, terrestrial, air). Currently, there is great concern about the exposition and impact on animal health, including humans, because of the effects of ingestion and accumulation of these nanomaterials (NMs) in aquatic organisms and their incorporation into the food chain. NPs´ mechanisms of action on humans are currently unknown. In this study, we evaluated the altered molecular mechanisms on human neural stem cell line (hNS1) after 4 days of exposure to 30 nm polystyrene (PS) NPs (0.5, 2.5 and 10 μg/mL). Our results showed that NPs can induce oxidative stress, cellular stress, DNA damage, alterations in inflammatory response, and apoptosis, which could lead to tissue damage and neurodevelopmental diseases.Publication Multiepitope Dendrimeric Antigen-Silica Particle Composites as Nano-Based Platforms for Specific Recognition of IgEs(Frontiers Media, 2021-12-03) Gil-Ocaña, Violeta; Jimenez, Isabel M.; Mayorga, Cristobalina; Doña, Inmaculada; Céspedes, Jose Antonio; Montañez, Maria I.; Vida, Yolanda; Torres, Maria J.; Perez-Inestrosa, Ezequiel; [Gil-Ocaña,V; Vida,Y; Perez-Inestrosa,E] Universidad de Málaga-Instituto de Investigación Biomédica de Málaga (IBIMA), Dpto. Química Orgánica, Málaga, Spain. [Gil-Ocaña,V; Mayorga,C; Montañez,MI; Vida,Y; Torres,MJ; Perez-Inestrosa,E] Centro Andaluz de Nanomedicina y Biotecnología-BIONAND, Parque Tecnológico de Andalucía, Málaga, Spain. [Jimenez,IM; Mayorga,C; Doña,I; Céspedes,JA.; Montañez,MI; Vida,Y; Torres,MJ] Allergy Research Group, Instituto de Investigación Biomédica de Málaga-Instituto de Investigación Biomédica de Málaga (IBIMA), Málaga, Spain. [Jimenez,IM; Mayorga,C; Doña,I; Montañez,MI; Vida,Y; Torres,MJ] Allergy Unit, Hospital Regional Universitario de Málaga, Málaga, Spain. [Torres,MJ] Universidad de Málaga-Instituto de Investigación Biomédica de Málaga (IBIMA), Dpto. Medicina, Málaga, Spain.β-lactam antibiotics (BLs) are the drugs most frequently involved in drug hypersensitivity reactions. However, current in vitro diagnostic tests have limited sensitivity, partly due to a poor understanding of in vivo drug-protein conjugates that both induce the reactions and are immunologically recognized. Dendrimeric Antigen-Silica particle composites (DeAn@SiO2), consisting on nanoparticles decorated with BL-DeAns are promising candidates for improving the in vitro clinical diagnostic practice. In this nano-inspired system biology, the synthetic dendrimer plays the role of the natural carrier protein, emulating its haptenation by drugs and amplifying the multivalence. Herein, we present the design and synthesis of new multivalent mono- and bi-epitope DeAn@SiO2, using amoxicillin and/or benzylpenicillin allergenic determinants as ligands. The homogeneous composition of nanoparticles provides high reproducibility and quality, which is critical for in vitro applications. The suitable functionalization of nanoparticles allows the anchoring of DeAn, minimizing the nonspecific interactions and facilitating the effective exposure to specific IgE; while the larger interaction area increments the likelihood of capturing specific IgE. This achievement is particularly important for improving sensitivity of current immunoassays since IgE levels in BL allergic patients are very low. Our data suggest that these new nano-based platforms provide a suitable tool for testing IgE recognition to more than one BL simultaneously. Immunochemical studies evidence that mono and bi-epitope DeAn@SiO2 composites could potentially allow the diagnosis of patients allergic to any of these drugs with a single test. These organic-inorganic hybrid materials represent the basis for the development of a single screening for BL-allergies.Publication Multifunctional Magnetic and Upconverting Nanobeads as Dual Modal Imaging Tools(2017-11-02) Materia, Maria Elena; Pernia Leal, Manuel; Scotto, Marco; Balakrishnan, Preethi Bala; Kumar Avugadda, Sahitya; Garc�a-Mart�n, Mar�a L; Cohen, Bruce E; Chan, Emory M; Pellegrino, TeresaWe report the fabrication of aqueous multimodal imaging nanocomposites based on superparamagnetic nanoparticles (MNPs) and two different sizes of photoluminescent upconverting nanoparticles (UCNPs). The controlled and simultaneous incorporation of both types of nanoparticles (NPs) was obtained by controlling the solvent composition and the addition rate of the destabilizing solvent. The magnetic properties of the MNPs remained unaltered after their encapsulation into the polymeric beads as shown by the T2 relaxivity measurements. The UCNPs maintain photoluminescent properties even when embedded with the MNPs into the polymer bead. Moreover, the light emitted by the magnetic and upconverting nanobeads (MUCNBs) under NIR excitation (?exc = 980 nm) was clearly observed through different thicknesses of agarose gel or through a mouse skin layer. The comparison with magnetic and luminescent nanobeads based on red-emitting quantum dots (QDs) demonstrated that while the QD-based beads show significant autofluorescence background from the skin, the signal obtained by the MUCNBs allows a decrease in this background. In summary, these results indicate that MUCNBs are good magnetic and optical probes for in vivo multimodal imaging sensors.Publication Nano-Antagonist Alleviates Inflammation and Allows for MRI of Atherosclerosis.(2019) Mog, Brian; Asase, Courteney; Chaplin, Alice; Gao, Huiyun; Rajagopalan, Sanjay; Maiseyeu, AndreiSpecific targeting of inflammation remains a challenge in many pathologies, because of the necessary balance between host tolerance and efficacious inflammation resolution. Here, we discovered a short, 4-mer peptide which possesses antagonist properties towards CC chemokine receptor 2 (CCR2), but only when displayed on the surface of lipid nanoparticles. According to BLAST analysis, this peptide motif is a common repeating fragment in a number of proteins of the CC chemokine family, which are key players in the inflammatory response. In this study, self-assembled, peptide-conjugated nanoparticles (CCTV) exhibited typical properties of CCR2 antagonism, including affinity to the CCR2 receptor, inhibition of chemotactic migration of primary monocytes, and prevention from CC chemokine ligand 2 (CCL2)-induced actin polymerization. Furthermore, CCTV ameliorated NFkB activation and downregulated the secondary, but not the primary, inflammatory response in cultured macrophages. When conjugated with gadolinium or europium cryptates, CCTV enabled targeted imaging (via magnetic resonance imaging and time-resolved fluorescence) of atherosclerosis, a chronic inflammatory condition in which the CCL2/CCR2 axis is highly dysfunctional. CCTV targeted CCR2hiLy6Chi inflammatory monocytes in blood and the atherosclerotic plaque, resulting in cell-specific transcriptional downregulation of key inflammatory genes. Finally, CCTV generated pronounced inflammasome inactivation, likely mediated through reactive oxygen species scavenging and downregulation of NLRP3. In summary, our work demonstrates for the first time that a short peptide fragment presented on a nanoparticle surface exhibit potent receptor-targeted antagonist effects, which are not seen with the peptide alone. Unlike commonly used cargo-carrying, vector-directed drug delivery vehicles, CCTV nanoparticles may act as therapeutics/theranostics themselves, particularly in inflammatory conditions with CCL2/CCR2 pathogenesis, including cardiovascular disease and cancer.Publication Neurotoxicity and endocrine disruption caused by polystyrene nanoparticles in zebrafish embryo(Elsevier, 2023-05-20) Torres-Ruiz, Mónica; De Alba-González, Mercedes; Morales, Mónica; Martin-Folgar, Raquel; González-Caballero, MCarmen; Cañas Portilla, Ana Isabel; De la Vieja, Antonio; Ministerio de Ciencia e Innovación (España); Agencia Estatal de Investigación (España); Instituto de Salud Carlos III; National University of Distance Education (España)Nanoplastics (NP) are present in aquatic and terrestrial ecosystems. Humans can be exposed to them through contaminated water, food, air, or personal care products. Mechanisms of NP toxicity are largely unknown and the Zebrafish embryo poses an ideal model to investigate them due to its high homology with humans. Our objective in the present study was to combine a battery of behavioral assays with the study of endocrine related gene expression, to further explore potential NP neurotoxic effects on animal behavior. Polystyrene nanoplastics (PSNP) were used to evaluate NP toxicity. Our neurobehavioral profiles include a tail coiling assay, a light/dark activity assay, two thigmotaxis anxiety assays (auditory and visual stimuli), and a startle response - habituation assay in response to auditory stimuli. Results show PSNP accumulated in eyes, neuromasts, brain, and digestive system organs. PSNP inhibited acetylcholinesterase and altered endocrine-related gene expression profiles both in the thyroid and glucocorticoid axes. At the whole organism level, we observed altered behaviors such as increased activity and anxiety at lower doses and lethargy at a higher dose, which could be due to a variety of complex mechanisms ranging from sensory organ and central nervous system effects to others such as hormonal imbalances. In addition, we present a hypothetical adverse outcome pathway related to these effects. In conclusion, this study provides new understanding into NP toxic effects on zebrafish embryo, emphasizing a critical role of endocrine disruption in observed neurotoxic behavioral effects, and improving our understanding of their potential health risks to human populations.Publication New Insights in Therapy for Food Allergy(Multidisciplinary Digital Publishing Institute (MDPI), 2021-05-10) Mayorga, Cristobalina; Palomares, Francisca; Cañas, José A.; Pérez-Sánchez, Natalia; Núñez, Rafael; Torres, María José; Gómez, Francisca; [Mayorga,C; Palomares,F; Cañas,JA; Núñez,R] Allergy Research Group, Instituto de Investigación Biomédica de Málaga (IBIMA),Málaga, Spain. [Mayorga,C; Pérez-Sánchez,N; Torres,MJ; Gomez,F] Allergy Clinical Unit, Hospital Regional Universitario de Málaga, Málaga, Spain. [Torres,MJ] Medicine Department, Universidad de Málaga-UMA, Málaga, Spain.Food allergy is an increasing problem worldwide, with strict avoidance being classically the only available reliable treatment. The main objective of this review is to cover the latest information about the tools available for the diagnosis and treatment of food allergies. In recent years, many efforts have been made to better understand the humoral and cellular mechanisms involved in food allergy and to improve the strategies for diagnosis and treatment. This review illustrates IgE-mediated food hypersensitivity and provides a current description of the diagnostic strategies and advances in different treatments. Specific immunotherapy, including different routes of administration and new therapeutic approaches, such as hypoallergens and nanoparticles, are discussed in detail. Other treatments, such as biologics and microbiota, are also described. Therefore, we conclude that although important efforts have been made in improving therapies for food allergies, including innovative approaches mainly focusing on efficacy and safety, there is an urgent need to develop a set of basic and clinical results to help in the diagnosis and treatment of food allergies.Publication Oligonucleotide Sensor Based on Selective Capture of Upconversion Nanoparticles Triggered by Target-Induced DNA Interstrand Ligand Reaction(ACS Publications, 2017-03) Mendez-Gonzalez, Diego; Laurenti, Marco; Latorre, Alfonso; Somoza, Alvaro; Vazquez, Ana; Negredo, Anabel; López-Cabarcos, Enrique; Calderón, Oscar G.; Melle, Sonia; Rubio-Retama, Jorge; Ministerio de Economía y Competitividad (España); Bill & Melinda Gates Foundation; Asociación Española Contra el Cáncer; Banco Santander; Complutense University of Madrid (España)We present a sensor that exploits the phenomenon of upconversion luminescence to detect the presence of specific sequences of small oligonucleotides such as miRNAs among others. The sensor is based on NaYF4:Yb,Er@SiO2 nanoparticles functionalized with ssDNA that contain azide groups on the 3' ends. In the presence of a target sequence, interstrand ligation is possible via the click-reaction between one azide of the upconversion probe and a DBCO-ssDNA-biotin probe present in the solution. As a result of this specific and selective process, biotin is covalently attached to the surface of the upconversion nanoparticles. The presence of biotin on the surface of the nanoparticles allows their selective capture on a streptavidin-coated support, giving a luminescent signal proportional to the amount of target strands present in the test samples. With the aim of studying the analytical properties of the sensor, total RNA samples were extracted from healthy mosquitoes and were spiked-in with a specific target sequence at different concentrations. The result of these experiments revealed that the sensor was able to detect 10-17 moles per well (100 fM) of the target sequence in mixtures containing 100 ng of total RNA per well. A similar limit of detection was found for spiked human serum samples, demonstrating the suitability of the sensor for detecting specific sequences of small oligonucleotides under real conditions. In contrast, in the presence of noncomplementary sequences or sequences having mismatches, the luminescent signal was negligible or conspicuously reduced.Publication Remodeling arteries: studying the mechanical properties of 3D-bioprinted hybrid photoresponsive materials.(Royal Society of Chemistry (RSC), 2023-10-11) Aizarna-Lopetegui, Uxue; García-Astrain, Clara; Renero-Lecuna, Carlos; González-Callejo, Patricia; Villaluenga, Irune; del Pozo, Miguel Angel; Sánchez-Álvarez, Miguel; Henriksen-Lacey, Malou; Jimenez de Aberasturi, Dorleta3D-printed cell models are currently in the spotlight of medical research. Whilst significant advances have been made, there are still aspects that require attention to achieve more realistic models which faithfully represent the in vivo environment. In this work we describe the production of an artery model with cyclic expansive properties, capable of mimicking the different physical forces and stress factors that cells experience in physiological conditions. The artery wall components are reproduced using 3D printing of thermoresponsive polymers with inorganic nanoparticles (NPs) representing the outer tunica adventitia, smooth muscle cells embedded in extracellular matrix representing the tunica media, and finally a monolayer of endothelial cells as the tunica intima. Cyclic expansion can be induced thanks to the inclusion of photo-responsive plasmonic NPs embedded within the thermoresponsive ink composition, resulting in changes in the thermoresponsive polymer hydration state and hence volume, in a stimulated on-off manner. By changing the thermoresponsive polymer composition, the transition temperature and pulsatility can be efficiently tuned. We show the direct effect of cyclic expansion and contraction on the overlying cell layers by analyzing transcriptional changes in mechanoresponsive mesenchymal genes associated with such microenvironmental physical cues. The technique described herein involving stimuli-responsive 3D printed tissue constructs, also described as four- dimensional (4D) printing, offers a novel approach for the production of dynamic biomodels.Publication Sphingomyelinase-responsive nanomicelles for targeting atherosclerosis.(Royal Society of Chemistry (RSC), 2024-03-28) Muñoz-Hernando, María; Nogales, Paula; Fernández-Barahona, Irene; Ruiz-Cabello, Jesús; Bentzon, Jacob F; Herranz, Fernando; Ministerio de Economía, Industria y Competitividad (España); Unión Europea. Fondo Europeo de Desarrollo Regional (FEDER/ERDF); Ministerio de Ciencia e Innovación (España); Comunidad de Madrid (España); Fundación La Caixa; Fundación ProCNICAtherosclerosis, a leading cause of cardiovascular diseases requires approaches to enhance disease monitoring and treatment. Nanoparticles offer promising potential in this area by being customisable to target components or molecular processes within plaques, while carrying diagnostic and therapeutic agents. However, the number of biomarkers available to target this disease is limited. This study investigated the use of sphingomyelin-based nanomicelles triggered by sphingomyelinase (SMase) in atherosclerotic plaques. Accumulation of iron oxide-based nanomicelles in the plaque was demonstrated by fluorescence, MR imaging and electron microscopy. These findings demonstrate the possibility of utilising SMase as a mechanism to retain nanoprobes within plaques, thus opening up possibilities for future therapeutic interventions.Publication Synthesis of a theranostic platform based on fibrous silica nanoparticles for the enhanced treatment of triple-negative breast cancer promoted by a combination of chemotherapeutic agents.(Elsevier, 2022-06) Ovejero-Paredes, Karina; Díaz-García, Diana; Mena-Palomo, Irene; Marciello, Marzia; Lozano-Chamizo, Laura; Morato, Yurena Luengo; Prashar, Sanjiv; Gómez-Ruiz, Santiago; Filice, Marco; Ministerio de Ciencia e Innovación (España); Ministerio de Ciencia, Innovación y Universidades (España); Unión Europea. Fondo Europeo de Desarrollo Regional (FEDER/ERDF); Comunidad de Madrid (España); Instituto de Salud Carlos III; Ministerio de Ciencia e Innovación. Centro de Excelencia Severo Ochoa (España)A new series of theranostic silica materials based on fibrous silica particles acting as nanocarriers of two different cytotoxic agents, namely, chlorambucil and an organotin metallodrug have been prepared and structurally characterized. Besides the combined therapeutic activity, these platforms have been decorated with a targeting molecule (folic acid, to selectively target triple negative breast cancer) and a molecular imaging agent (Alexa Fluor 647, to enable their tracking both in vitro and in vivo). The in vitro behaviour of the multifunctional silica systems showed a synergistic activity of the two chemotherapeutic agents in the form of an enhanced cytotoxicity against MDA-MB-231 cells (triple negative breast cancer) as well as by a higher cell migration inhibition. Subsequently, the in vivo applicability of the siliceous nanotheranostics was successfully assessed by observing with in vivo optical imaging techniques a selective tumour accumulation (targeting ability), a marked inhibition of tumour growth paired to a marked antiangiogenic ability after 13 days of systemic administration, thus, confirming the enhanced theranostic activity. The systemic nanotoxicity was also evaluated by analyzing specific biochemical markers. The results showed a positive effect in form of reduced cytotoxicity when both chemotherapeutics are administered in combination thanks to the fibrous silica nanoparticles. Overall, our results confirm the promising applicability of these novel silica-based nanoplatforms as advanced drug-delivery systems for the synergistic theranosis of triple negative breast cancer.