Nanocarrier Lipid Composition Modulates the Impact of Pulmonary Surfactant Protein B (SP-B) on Cellular Delivery of siRNA
Roberta Guagliardo,
Pieterjan Merckx,
Agata Zamborlin,
Lynn De Backer,
Mercedes Echaide,
Jesus Pérez-Gil,
Stefaan C. De Smedt,
Koen Raemdonck
Affiliations
Roberta Guagliardo
Ghent Research Group on Nanomedicines, Laboratory of General Biochemistry and Physical Pharmacy, Department of Pharmaceutics, Ghent University, Ottergemsesteenweg 460, 9000 Ghent, Belgium
Pieterjan Merckx
Ghent Research Group on Nanomedicines, Laboratory of General Biochemistry and Physical Pharmacy, Department of Pharmaceutics, Ghent University, Ottergemsesteenweg 460, 9000 Ghent, Belgium
Agata Zamborlin
Ghent Research Group on Nanomedicines, Laboratory of General Biochemistry and Physical Pharmacy, Department of Pharmaceutics, Ghent University, Ottergemsesteenweg 460, 9000 Ghent, Belgium
Lynn De Backer
Ghent Research Group on Nanomedicines, Laboratory of General Biochemistry and Physical Pharmacy, Department of Pharmaceutics, Ghent University, Ottergemsesteenweg 460, 9000 Ghent, Belgium
Mercedes Echaide
Departamento de Bioquímica y Biología Molecular, Facultad de Biologia, and Research Institute Hospital 12 de Octubre, Universidad Complutense, José Antonio Novais 12, 28040 Madrid, Spain
Jesus Pérez-Gil
Departamento de Bioquímica y Biología Molecular, Facultad de Biologia, and Research Institute Hospital 12 de Octubre, Universidad Complutense, José Antonio Novais 12, 28040 Madrid, Spain
Stefaan C. De Smedt
Ghent Research Group on Nanomedicines, Laboratory of General Biochemistry and Physical Pharmacy, Department of Pharmaceutics, Ghent University, Ottergemsesteenweg 460, 9000 Ghent, Belgium
Koen Raemdonck
Ghent Research Group on Nanomedicines, Laboratory of General Biochemistry and Physical Pharmacy, Department of Pharmaceutics, Ghent University, Ottergemsesteenweg 460, 9000 Ghent, Belgium
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.
