RT Journal Article
T1 Nanocarrier lipid composition modulates the impact of pulmonary surfactant protein B (SP-B) on cellular delivery of siRNA
A1 Guagliardo, Roberta
A1 Merckx, Pieterjan
A1 Zamborlin, Agata
A1 Backer, Lynn de
A1 Echaide Torreguitar, Mercedes
A1 Pérez-Gil, Jesús
A1 Smedt, Stefaan C. de
A1 Raemdonck, Koen
AB 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.
PB MDPI
SN 1999-4923, ESSN: 1999-4923
YR 2019
FD 2019-08-23
LK https://hdl.handle.net/20.500.14352/13473
UL https://hdl.handle.net/20.500.14352/13473
LA eng
NO Unión Europea. H2020
NO Ministerio de Economía y Competitividad (MINECO)
NO Comunidad de Madrid
NO Ghent University (Belgium)
NO Agency for Innovation by Science and Technology Flanders (IWT)
NO Research Foundation - Flanders (FWO)
DS Docta Complutense
RD 5 abr 2025