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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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Guagliardo, Roberta and Merckx, Pieterjan and Zamborlin, Agata and Backer, Lynn de and Echaide, 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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Official URL: https://www.mdpi.com/1999-4923/11/9/431://link.springer.com/article/10.1007/s00284-019-01759-9



Abstract

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:07 Oct 2019 12:05

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