Nanocarrier lipid composition modulates the impact of pulmonary surfactant protein B (SP-B) on cellular delivery of siRNA



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Guagliardo, Roberta and Merckx, Pieterjan and Zamborlin, Agata and Backer, Lynn de and Echaide Torreguitar, Mercedes and Pérez-Gil, Jesús and Smedt, Stefaan C. de and Raemdonck, Koen (2019) Nanocarrier lipid composition modulates the impact of pulmonary surfactant protein B (SP-B) on cellular delivery of siRNA. Pharmaceutics, 11 (9). pp. 1-16. ISSN 1999-4923, ESSN: 1999-4923

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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.

Item Type:Article
Uncontrolled Keywords:siRNA delivery; Nanoparticles; Pulmonary surfactant
Subjects:Medical sciences > Biology > Molecular biology
Medical sciences > Biology > Biochemistry
ID Code:56587
Deposited On:07 Oct 2019 11:09
Last Modified:31 May 2021 10:19

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