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
3 results
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Now showing 1 - 3 of 3
Item Insights into the mechanisms of interaction between inhalable lipid-polymer hybrid nanoparticles and pulmonary surfactant(Journal of Colloid and Interface Science, 2022) Xu, You; Parra-Ortiz, Elisa; Wan, Feng; Cañadas Benito, Olga; García Álvarez, María Begoña; Thakur, Aneesh; Franzyk, Henrik; Pérez Gil, Jesús; Malmsten, Martin; Foged, CamillaPulmonary delivery of small interfering RNA (siRNA) using nanoparticle-based delivery systems is promising for local treatment of respiratory diseases. We designed dry powder inhaler formulations of siRNA-loaded lipid-polymer hybrid nanoparticles (LPNs) with aerosolization properties optimized for inhalation therapy. Interactions between LPNs and pulmonary surfactant (PS) determine the fate of inhaled LPNs, but interaction mechanisms are unknown. Here we used surface-sensitive techniques to study how physicochemical properties and pathological microenvironments influence interactions between siRNA-loaded LPNs and supported PS layers. PS was deposited on SiO2 surfaces as single bilayer or multilayers and characterized using quartz crystal microbalance with dissipation monitoring and Fourier-transform infrared spectroscopy with attenuated total reflection. Immobilization of PS as multilayers, resembling the structural PS organization in the alveolar subphase, effectively reduced the relative importance of interactions between PS and the underlying surface. However, the binding affinity between PS and LPNs was identical in the two models. The physicochemical LPN properties influenced the translocation pathways and retention time of LPNs. Membrane fluidity and electrostatic interactions were decisive for the interaction strength between LPNs and PS. Experimental conditions reflecting pathological microenvironments promoted LPN deposition. Hence, these results shed new light on design criteria for LPN transport through the air–blood barrier.Item Uptake of nanoparticles by alveolar macrophages is triggered by surfactant protein A(Nanomedicine: Nanotechnology, Biology and Medicine, 2011) Ruge, Christian Arnold; Kirch, Julian; Cañadas Benito, Olga; Schneider, Marc; Pérez Gil, Jesús; Schaefer, Ulrich Friedrich; Casals Carro, María Cristina; Lehr, Claus MichaelUnderstanding the bio-nano interactions in the lungs upon the inhalation of nanoparticles is a major challenge in both pulmonary nanomedicine and nanotoxicology. To investigate the effect of pulmonary surfactant protein A (SP-A) on the interaction between nanoparticles and alveolar macrophages, we used magnetite nanoparticles (110-180 nm in diameter) coated with different polymers (starch, carboxymethyldextran, chitosan, poly-maleic-oleic acid, phosphatidylcholine). Cellular binding and uptake of nanoparticles by alveolar macrophages was increased for nanoparticles treated with SP-A, whereas albumin, the prevailing protein in plasma, led to a significant decrease. A significantly different adsorption pattern of SP-A, compared to albumin was found for these five different nanomaterials. This study provides evidence that after inhalation of nanoparticles, a different protein coating and thus different biological behavior may result compared to direct administration to the bloodstreamItem The interplay of lung surfactant proteins and lipids assimilates the macrophage clearance of nanoparticles(PLoS One, 2012) Ruge, C.A.; Schaefer, U.F.; Herrmann, J.; Kirch, J.; Cañadas Benito, Olga; Echaide Torreguitar, Mercedes; Pérez Gil, Jesús; Casals Carro, María Jesús; Müller, R.; Lehr, C.M.The peripheral lungs are a potential entrance portal for nanoparticles into the human body due to their large surface area. The fact that nanoparticles can be deposited in the alveolar region of the lungs is of interest for pulmonary drug delivery strategies and is of equal importance for toxicological considerations. Therefore, a detailed understanding of nanoparticle interaction with the structures of this largest and most sensitive part of the lungs is important for both nanomedicine and nanotoxicology. Astonishingly, there is still little known about the bio-nano interactions that occur after nanoparticle deposition in the alveoli. In this study, we compared the effects of surfactant-associated protein A (SP-A) and D (SP-D) on the clearance of magnetite nanoparticles (mNP) with either more hydrophilic (starch) or hydrophobic (phosphatidylcholine) surface modification by an alveolar macrophage (AM) cell line (MH-S) using flow cytometry and confocal microscopy. Both proteins enhanced the AM uptake of mNP compared with pristine nanoparticles; for the hydrophilic ST-mNP, this effect was strongest with SP-D, whereas for the hydrophobic PL-mNP it was most pronounced with SP-A. Using gel electrophoretic and dynamic light scattering methods, we were able to demonstrate that the observed cellular effects were related to protein adsorption and to protein-mediated interference with the colloidal stability. Next, we investigated the influence of various surfactant lipids on nanoparticle uptake by AM because lipids are the major surfactant component. Synthetic surfactant lipid and isolated native surfactant preparations significantly modulated the effects exerted by SP-A and SP-D, respectively, resulting in comparable levels of macrophage interaction for both hydrophilic and hydrophobic nanoparticles. Our findings suggest that because of the interplay of both surfactant lipids and proteins, the AM clearance of nanoparticles is essentially the same, regardless of different intrinsic surface properties.