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

Roberta Guagliardo, Pieterjan Merckx (UGent) , Agata Zamborlin (UGent) , Lynn De Backer (UGent) , Mercedes Echaide, Jesus Pérez-Gil, Stefaan De Smedt (UGent) and Koen Raemdonck (UGent)
(2019) PHARMACEUTICS. 11(9).
Author
Organization
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.
Keywords
siRNA delivery, nanoparticles, pulmonary surfactant, BIODEGRADABLE DEXTRAN NANOGELS, SP-C, GLYCIDYL METHACRYLATE, RATIONAL DESIGN, NANOPARTICLES, CHALLENGES, STABILITY, PEPTIDE, MODEL

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Citation

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MLA
Guagliardo, Roberta, et al. “Nanocarrier Lipid Composition Modulates the Impact of Pulmonary Surfactant Protein B (SP-B) on Cellular Delivery of SiRNA.” PHARMACEUTICS, vol. 11, no. 9, 2019, doi:10.3390/pharmaceutics11090431.
APA
Guagliardo, R., Merckx, P., Zamborlin, A., De Backer, L., Echaide, M., Pérez-Gil, J., … Raemdonck, K. (2019). Nanocarrier lipid composition modulates the impact of pulmonary surfactant protein B (SP-B) on cellular delivery of siRNA. PHARMACEUTICS, 11(9). https://doi.org/10.3390/pharmaceutics11090431
Chicago author-date
Guagliardo, Roberta, Pieterjan Merckx, Agata Zamborlin, Lynn De Backer, Mercedes Echaide, Jesus Pérez-Gil, Stefaan De Smedt, and Koen Raemdonck. 2019. “Nanocarrier Lipid Composition Modulates the Impact of Pulmonary Surfactant Protein B (SP-B) on Cellular Delivery of SiRNA.” PHARMACEUTICS 11 (9). https://doi.org/10.3390/pharmaceutics11090431.
Chicago author-date (all authors)
Guagliardo, Roberta, Pieterjan Merckx, Agata Zamborlin, Lynn De Backer, Mercedes Echaide, Jesus Pérez-Gil, Stefaan De Smedt, and Koen Raemdonck. 2019. “Nanocarrier Lipid Composition Modulates the Impact of Pulmonary Surfactant Protein B (SP-B) on Cellular Delivery of SiRNA.” PHARMACEUTICS 11 (9). doi:10.3390/pharmaceutics11090431.
Vancouver
1.
Guagliardo R, Merckx P, Zamborlin A, De Backer L, Echaide M, Pérez-Gil J, et al. Nanocarrier lipid composition modulates the impact of pulmonary surfactant protein B (SP-B) on cellular delivery of siRNA. PHARMACEUTICS. 2019;11(9).
IEEE
[1]
R. Guagliardo et al., “Nanocarrier lipid composition modulates the impact of pulmonary surfactant protein B (SP-B) on cellular delivery of siRNA,” PHARMACEUTICS, vol. 11, no. 9, 2019.
@article{8643987,
  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.}},
  articleno    = {{431}},
  author       = {{Guagliardo, Roberta and Merckx, Pieterjan and Zamborlin, Agata and De Backer, Lynn and Echaide, Mercedes and Pérez-Gil, Jesus and De Smedt, Stefaan and Raemdonck, Koen}},
  issn         = {{1999-4923}},
  journal      = {{PHARMACEUTICS}},
  keywords     = {{siRNA delivery,nanoparticles,pulmonary surfactant,BIODEGRADABLE DEXTRAN NANOGELS,SP-C,GLYCIDYL METHACRYLATE,RATIONAL DESIGN,NANOPARTICLES,CHALLENGES,STABILITY,PEPTIDE,MODEL}},
  language     = {{eng}},
  number       = {{9}},
  pages        = {{16}},
  title        = {{Nanocarrier lipid composition modulates the impact of pulmonary surfactant protein B (SP-B) on cellular delivery of siRNA}},
  url          = {{http://doi.org/10.3390/pharmaceutics11090431}},
  volume       = {{11}},
  year         = {{2019}},
}
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