Person: Cañadas Benito, Olga
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First Name
Olga
Last Name
Cañadas Benito
Affiliation
Universidad Complutense de Madrid
Faculty / Institute
Ciencias Biológicas
Department
Bioquímica y Biología Molecular
Area
Bioquímica y Biología Molecular
Identifiers
5 results
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Now showing 1 - 5 of 5
Item Delayed alveolar clearance of nanoparticles through control of coating composition and interaction with lung surfactant protein A(Materials Science & Engineering C, 2021) Carregal Romero, Susana; Groult, Hugo; Cañadas Benito, Olga; A-Gonzalez, Noelia; Lechuga Vieco, Ana Victoria; García Fojeda, Belén; Herranz, Fernando; Pellico, Juan; Hidalgo, Andrés; Casals, Cristina; Ruiz Cabello, JesúsThe coating composition of nanomedicines is one of the main features in determining the medicines' fate, clearance, and immunoresponse in the body. To highlight the coatings' impact in pulmonary administration, two micellar superparamagnetic iron oxide nanoparticles (SPION) were compared. These nanoparticles are similar in size and charge but have different coatings: either phosphatidylcholine (PC-SPION) or bovine serum albumin (BSA-SPION). The aim of the study was to increase the understanding of the nano-bio interaction with the cellular and non-cellular components of the lung and underline valuable coatings either for local lung-targeted drug delivery in theranostic application or patient-friendly route systemic administration. PC-SPION and BSA-SPION were deposited in the alveoli by in vivo instillation and, despite the complexity of imaging the lung, SPION were macroscopically visualized by MRI. Impressively, PC-SPION were retained within the lungs for at least a week, while BSA-SPION were cleared more rapidly. The different lung residence times were confirmed by histological analysis and supported by a flow cytometry analysis of the SPION interactions with different myeloid cell populations. To further comprehend the way in which these nanoformulations interact with lung components at the molecular level, we used fluorescence spectroscopy, turbidity measurements, and dynamic light scattering to evaluate the interactions of the two SPION with surfactant protein A (SP-A), a key protein in setting up the nanoparticle behavior in the alveolar fluid. We found that SP-A induced aggregation of PC-SPION, but not BSA-SPION, which likely caused PC-SPION retention in the lung without inducing inflammation. In conclusion, the two SPION show different outcomes from interaction with SP-A leading to distinctive fate in the lung. PC-SPION hold great promise as imaging and theranostic agents when prolonged pulmonary drug delivery is required.Item Polyhydroxyalkanoate nanoparticles for pulmonary drug delivery: interaction with lung surfactant(Nanomaterials, 2021) Cañadas Benito, Olga; García-García, Andrea; Prieto, M. Auxiliadora; Pérez-Gil, JesúsPolyhydroxyalkanoates (PHA) are polyesters produced intracellularly by many bacterial species as energy storage materials, which are used in biomedical applications, including drug delivery systems, due to their biocompatibility and biodegradability. In this study, we evaluated the potential application of this nanomaterial as a basis of inhaled drug delivery systems. To that end, we assessed the possible interaction between PHA nanoparticles (NPs) and pulmonary surfactant using dynamic light scattering, Langmuir balances, and epifluorescence microscopy. Our results demonstrate that NPs deposited onto preformed monolayers of DPPC or DPPC/POPG bind these surfactant lipids. This interaction facilitated the translocation of the nanomaterial towards the aqueous subphase, with the subsequent loss of lipid from the interface. NPs that remained at the interface associated with liquid expanded (LE)/tilted condensed (TC) phase boundaries, decreasing the size of condensed domains and promoting the intermixing of TC and LE phases at submicroscopic scale. This provided the stability necessary for attaining high surface pressures upon compression, countering the destabilization induced by lipid loss. These effects were observed only for high NP loads, suggesting a limit for the use of these NPs in pulmonary drug delivery.Item Synergistic action of antimicrobial lung proteins against Klebsiella pneumoniae(International Journal of Molecular Sciences, 2021) Fraile Ágreda, Víctor; Cañadas Benito, Olga; Weaver, Timothy E.; Casals Carro, CristinaAs key components of innate immunity, lung antimicrobial proteins play a critical role in warding off invading respiratory pathogens. Lung surfactant protein A (SP-A) exerts synergistic antimicrobial activity with the N-terminal segment of the SP-B proprotein (SP-BN) against Klebsiella pneumoniae K2 in vivo. However, the factors that govern SP-A/SP-BN antimicrobial activity are still unclear. The aim of this study was to identify the mechanisms by which SP-A and SP-BN act synergistically against K. pneumoniae, which is resistant to either protein alone. The effect of these proteins on K. pneumoniae was studied by membrane permeabilization and depolarization assays and transmission electron microscopy. Their effects on model membranes of the outer and inner bacterial membranes were analyzed by differential scanning calorimetry and membrane leakage assays. Our results indicate that the SP-A/SP-BN complex alters the ultrastructure of K. pneumoniae by binding to lipopolysaccharide molecules present in the outer membrane, forming packing defects in the membrane that may favor the translocation of both proteins to the periplasmic space. The SP-A/SP-BN complex depolarized and permeabilized the inner membrane, perhaps through the induction of toroidal pores. We conclude that the synergistic antimicrobial activity of SP-A/SP-BN is based on the capability of this complex, but not either protein alone, to alter the integrity of bacterial membranes.Item Lipid–protein and protein–protein interactions in the pulmonary surfactant system and their role in lung homeostasis(International Journal of Molecular Sciences, 2020) Cañadas Benito, Olga; Olmeda Lozano, Bárbara; Alonso Eugenio, Alejandro; Pérez-Gil, JesúsPulmonary surfactant is a lipid/protein complex synthesized by the alveolar epithelium and secreted into the airspaces, where it coats and protects the large respiratory air–liquid interface. Surfactant, assembled as a complex network of membranous structures, integrates elements in charge of reducing surface tension to a minimum along the breathing cycle, thus maintaining a large surface open to gas exchange and also protecting the lung and the body from the entrance of a myriad of potentially pathogenic entities. Different molecules in the surfactant establish a multivalent crosstalk with the epithelium, the immune system and the lung microbiota, constituting a crucial platform to sustain homeostasis, under health and disease. This review summarizes some of the most important molecules and interactions within lung surfactant and how multiple lipid–protein and protein–protein interactions contribute to the proper maintenance of an operative respiratory surface.- Project number: 163
Item The Phantom Menace: Cómo salvar el mundo de una pandemia mediante Ingeniería Genética cooperativa(2021) Navarro LLorens, Juana María; Baldanta Callejo, Sara; Bénitez Prian, Mario; Blázquez Ortiz, Cristina; Bruñen Alfaro, Francisco; Cañadas Benito, Olga; Chinarro Sánchez, Adrián; García de la Camacha Selgas, Nuria; García-Fojeda García-Valdecasas, María Belén; Guevara Acosta, Flor Govinda; Leaño Hinojosa, Ariana; López Conejo, Maria Teresa; Lorente Pérez, Maria del Mar; Nogués Vera, Laura; Penalba Iglesias, Diana; Raisman, Andrea; Ranz Valdecasa, Maria Regina; Ruiz Ortega, Marta; Sánchez-Escalonilla Relea, Jose luis; Velasco Díez, Guillermo; Sánchez Torralba, AntonioEl año pasado se llevó a cabo un proyecto de innovación (PIMCD-2019 174) basado en el modelo pedagógico de la clase invertida o “Flipped Classroom” y en el juego de mesa PANDEMIC (ASMODEE IBÉRICA). Brevemente, este proyecto consistió en una propuesta didáctica sobre los contenidos de FIGG en el que tomando como partida un entorno lúdico, los alumnos de FIGG en equipos preparaban contenidos y reforzaban conocimientos adquiridos en clase. Para llevarlo a cabo, a los alumnos se les planteaba una hipotética situación en la que cuatro enfermedades mortales aparecen en la tierra. Los alumnos divididos en equipos de 5 personas, deben cooperar desarrollando una serie de acciones que les permitan ir conociendo a qué patógeno se enfrentan y desarrollar herramientas que les permita controlar la epidemia dentro de un tiempo dado. Así cada equipo debe frenar el avance de las infecciones y a la vez encontrar una cura para la misma. Curiosamente, todo este escenario fue planteado antes de que la crisis del COVID-19 impactara en nuestra sociedad. En cualquier caso, la situación vivida en los últimos meses ha motivado a los estudiantes de FIGG por lo que en su mayor parte han participado en su desarrollo de manera entusiasta. En este nuevo proyecto, hemos tomado como base el proyecto del curso pasado, pero introduciendo algunos elementos innovadores. Entre estas innovaciones destaca la incorporación de dos alumnos por grupo de FIGG que ya lo hubieran realizado en la edición pasada por cada uno de los grupos de FIGG como mentores.