Guagliardo, RobertaMerckx, PieterjanZamborlin, AgataBacker, Lynn deEchaide Torreguitar, MercedesPérez-Gil, JesúsSmedt, Stefaan C. deRaemdonck, Koen2023-06-172023-06-172019-08-231999-4923, ESSN: 1999-492310.3390/pharmaceutics11090431https://hdl.handle.net/20.500.14352/13473Two 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.engAtribución-NoComercial 3.0 Españajournal articlehttps://www.mdpi.com/1999-4923/11/9/431://link.springer.com/article/10.1007/s00284-019-01759-9open access577.112577.21siRNA deliveryNanoparticlesPulmonary surfactantBiología molecular (Biología)Bioquímica (Biología)2415 Biología Molecular2302 Bioquímica