Nanocarrier Lipid Composition Modulates the Impact of Pulmonary Surfactant Protein B (SP-B) on Cellular Delivery of siRNA
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 enc...
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| Format: | Article |
| Language: | English |
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MDPI AG
2019-08-01
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| Series: | Pharmaceutics |
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| Online Access: | https://www.mdpi.com/1999-4923/11/9/431 |
| _version_ | 1811263280034873344 |
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| author | Roberta Guagliardo Pieterjan Merckx Agata Zamborlin Lynn De Backer Mercedes Echaide Jesus Pérez-Gil Stefaan C. De Smedt Koen Raemdonck |
| author_facet | Roberta Guagliardo Pieterjan Merckx Agata Zamborlin Lynn De Backer Mercedes Echaide Jesus Pérez-Gil Stefaan C. De Smedt Koen Raemdonck |
| author_sort | Roberta Guagliardo |
| collection | DOAJ |
| description | 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. |
| first_indexed | 2024-04-12T19:42:50Z |
| format | Article |
| id | doaj.art-365b0f600804478bbe71c4ba8dbbceb5 |
| institution | Directory Open Access Journal |
| issn | 1999-4923 |
| language | English |
| last_indexed | 2024-04-12T19:42:50Z |
| publishDate | 2019-08-01 |
| publisher | MDPI AG |
| record_format | Article |
| series | Pharmaceutics |
| spelling | doaj.art-365b0f600804478bbe71c4ba8dbbceb52022-12-22T03:19:02ZengMDPI AGPharmaceutics1999-49232019-08-0111943110.3390/pharmaceutics11090431pharmaceutics11090431Nanocarrier Lipid Composition Modulates the Impact of Pulmonary Surfactant Protein B (SP-B) on Cellular Delivery of siRNARoberta Guagliardo0Pieterjan Merckx1Agata Zamborlin2Lynn De Backer3Mercedes Echaide4Jesus Pérez-Gil5Stefaan C. De Smedt6Koen Raemdonck7Ghent Research Group on Nanomedicines, Laboratory of General Biochemistry and Physical Pharmacy, Department of Pharmaceutics, Ghent University, Ottergemsesteenweg 460, 9000 Ghent, BelgiumGhent Research Group on Nanomedicines, Laboratory of General Biochemistry and Physical Pharmacy, Department of Pharmaceutics, Ghent University, Ottergemsesteenweg 460, 9000 Ghent, BelgiumGhent Research Group on Nanomedicines, Laboratory of General Biochemistry and Physical Pharmacy, Department of Pharmaceutics, Ghent University, Ottergemsesteenweg 460, 9000 Ghent, BelgiumGhent Research Group on Nanomedicines, Laboratory of General Biochemistry and Physical Pharmacy, Department of Pharmaceutics, Ghent University, Ottergemsesteenweg 460, 9000 Ghent, BelgiumDepartamento de Bioquímica y Biología Molecular, Facultad de Biologia, and Research Institute Hospital 12 de Octubre, Universidad Complutense, José Antonio Novais 12, 28040 Madrid, SpainDepartamento de Bioquímica y Biología Molecular, Facultad de Biologia, and Research Institute Hospital 12 de Octubre, Universidad Complutense, José Antonio Novais 12, 28040 Madrid, SpainGhent Research Group on Nanomedicines, Laboratory of General Biochemistry and Physical Pharmacy, Department of Pharmaceutics, Ghent University, Ottergemsesteenweg 460, 9000 Ghent, BelgiumGhent Research Group on Nanomedicines, Laboratory of General Biochemistry and Physical Pharmacy, Department of Pharmaceutics, Ghent University, Ottergemsesteenweg 460, 9000 Ghent, BelgiumTwo 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.https://www.mdpi.com/1999-4923/11/9/431siRNA deliverynanoparticlespulmonary surfactant |
| spellingShingle | Roberta Guagliardo Pieterjan Merckx Agata Zamborlin Lynn De Backer Mercedes Echaide Jesus Pérez-Gil Stefaan C. De Smedt Koen Raemdonck Nanocarrier Lipid Composition Modulates the Impact of Pulmonary Surfactant Protein B (SP-B) on Cellular Delivery of siRNA Pharmaceutics siRNA delivery nanoparticles pulmonary surfactant |
| title | Nanocarrier Lipid Composition Modulates the Impact of Pulmonary Surfactant Protein B (SP-B) on Cellular Delivery of siRNA |
| title_full | Nanocarrier Lipid Composition Modulates the Impact of Pulmonary Surfactant Protein B (SP-B) on Cellular Delivery of siRNA |
| title_fullStr | Nanocarrier Lipid Composition Modulates the Impact of Pulmonary Surfactant Protein B (SP-B) on Cellular Delivery of siRNA |
| title_full_unstemmed | Nanocarrier Lipid Composition Modulates the Impact of Pulmonary Surfactant Protein B (SP-B) on Cellular Delivery of siRNA |
| title_short | Nanocarrier Lipid Composition Modulates the Impact of Pulmonary Surfactant Protein B (SP-B) on Cellular Delivery of siRNA |
| title_sort | nanocarrier lipid composition modulates the impact of pulmonary surfactant protein b sp b on cellular delivery of sirna |
| topic | siRNA delivery nanoparticles pulmonary surfactant |
| url | https://www.mdpi.com/1999-4923/11/9/431 |
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