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Título:
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Nanocarrier lipid composition modulates the impact of pulmonary surfactant protein B (SP-B) on cellular delivery of siRNA
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Autores:
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Guagliardo, Roberta ;
Merckx, Pieterjan ;
Zamborlin, Agata ;
Backer, Lynn de ;
Echaide Torreguitar, Mercedes ;
Pérez Gil, Jesús ;
Smedt, Stefaan C. de ;
Raemdonck, Koen
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Tipo de documento:
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texto impreso
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Editorial:
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MDPI, 2019-08-23
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Dimensiones:
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application/pdf
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Nota general:
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cc_by_nc
info:eu-repo/semantics/openAccess
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Idiomas:
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Palabras clave:
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Estado = Publicado
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Materia = Ciencias Biomédicas: Biología: Biología molecular
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Materia = Ciencias Biomédicas: Biología: Bioquímica
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Tipo = Artículo
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Resumen:
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Two decades since the discovery of the RNA interference (RNAi) pathway, we are now witnessing the approval of the first RNAi-based treatments with small interfering RNA (siRNA) drugs. Nevertheless, the widespread use of siRNA is limited by various extra- and intracellular barriers, requiring its encapsulation in a suitable (nanosized) delivery system. On the intracellular level, the endosomal membrane is a major barrier following endocytosis of siRNA-loaded nanoparticles in target cells and innovative materials to promote cytosolic siRNA delivery are highly sought after. We previously identified the endogenous lung surfactant protein B (SP-B) as siRNA delivery enhancer when reconstituted in (proteo) lipid-coated nanogels. It is known that the surface-active function of SP-B in the lung is influenced by the lipid composition of the lung surfactant. Here, we investigated the role of the lipid component on the siRNA delivery-promoting activity of SP-B proteolipid-coated nanogels in more detail. Our results clearly indicate that SP-B prefers fluid membranes with cholesterol not exceeding physiological levels. In addition, SP-B retains its activity in the presence of different classes of anionic lipids. In contrast, comparable fractions of SP-B did not promote the siRNA delivery potential of DOTAP:DOPE cationic liposomes. Finally, we demonstrate that the beneficial effect of lung surfactant on siRNA delivery is not limited to lung-related cell types, providing broader therapeutic opportunities in other tissues as well.
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En línea:
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https://eprints.ucm.es/id/eprint/56587/1/Guagliardo%2C%20R.%20et%20al.%202019.%20Nanocarrier%20lipid%20composition....pdf
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