Nanocarrier Lipid Composition Modulates the Impact of Pulmonary Surfactant Protein B (SP-B) on Cellular Delivery of siRNA.

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ID: 38599
2019
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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.
Reference Key
guagliardo2019nanocarrierpharmaceutics Use this key to autocite in the manuscript while using SciMatic Manuscript Manager or Thesis Manager
Authors Guagliardo, Roberta;Merckx, Pieterjan;Zamborlin, Agata;De Backer, Lynn;Echaide, Mercedes;Pérez-Gil, Jesus;De Smedt, Stefaan C;Raemdonck, Koen;
Journal Pharmaceutics
Year 2019
DOI
E431
URL
Keywords
polycyclic aromatic hydrocarbons far eastern asia nitropolycyclic aromatic hydrocarbons urban air

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