PUBLICATION
Development of a Combined Lipid-Based Nanoparticle Formulation for Enhanced siRNA Delivery to Vascular Endothelial Cells
- Authors
- He, Y., Bi, D., Plantinga, J.A., Molema, G., Bussmann, J., Kamps, J.A.A.M.
- ID
- ZDB-PUB-221028-30
- Date
- 2022
- Source
- Pharmaceutics 14(10): (Journal)
- Registered Authors
- Bi, Dongdong, Bussmann, Jeroen
- Keywords
- cationic lipid formulation, endothelial cell delivery, lipid-based nanoparticles, siRNA therapy, zebrafish model
- MeSH Terms
- none
- PubMed
- 36297521 Full text @ Pharmaceutics
Citation
He, Y., Bi, D., Plantinga, J.A., Molema, G., Bussmann, J., Kamps, J.A.A.M. (2022) Development of a Combined Lipid-Based Nanoparticle Formulation for Enhanced siRNA Delivery to Vascular Endothelial Cells. Pharmaceutics. 14(10):.
Abstract
Low transfection efficiency in endothelial cells (EC) is still a bottleneck for the majority of siRNA-based vascular delivery approaches. In this work, we developed a lipid-based nanoparticle (LNP) formulation based on a combination of a permanently charged cationic lipid-DOTAP and a conditionally ionized cationic lipid-MC3 (DOTAP/MC3) for the enhanced delivery of siRNA into EC. Compared with a single DOTAP or MC3-based benchmark LNP, we demonstrated that the DOTAP/MC3 LNP formulation shows the best transfection efficiency both in primary EC in vitro and in endothelium in zebrafish. The high transfection activity of the DOTAP/MC3 LNP formulation is achieved by a combination of improved endothelial association mediated by DOTAP and MC3-triggered efficient siRNA intracellular release in EC. Furthermore, AbVCAM-1-coupled DOTAP/MC3 LNP-mediated siRNARelA transfection showed pronounced anti-inflammatory effects in inflammatory-activated primary EC by effectively blocking the NF-κB pathway. In conclusion, the combination of permanent and ionizable cationic lipids in LNP formulation provides an effective endothelial cell delivery of siRNA.
Genes / Markers
Expression
Phenotype
Mutations / Transgenics
Human Disease / Model
Sequence Targeting Reagents
Fish
Orthology
Engineered Foreign Genes
Mapping