1,397
Views
0
CrossRef citations to date
0
Altmetric
Research Articles

MC3/SAINT-O-Somes, a novel liposomal delivery system for efficient and safe delivery of siRNA into endothelial cells

, , , ORCID Icon & ORCID Icon
Pages 328-337 | Received 23 Dec 2022, Accepted 20 Feb 2023, Published online: 15 Mar 2023
 

Abstract

Increased understanding of chronic inflammatory diseases and the role of endothelial cell (EC) activation herein, have urged interest in sophisticated strategies to therapeutically intervene in activated EC to treat these diseases. Liposome-mediated delivery of therapeutic siRNA in inflammation-activated EC is such a strategy. In this study, we describe the design and characterisation of two liposomal siRNA delivery systems formulated with the cationic MC3 lipid or MC3/SAINT mixed lipids, referred to as MC3-O-Somes (MOS) and MC3/SAINT-O-Somes (MSS). The two formulations showed comparable physicochemical properties, except for better siRNA encapsulation efficiency in the MSS formulation. Antibody-mediated VCAM-1 targeting (AbVCAM-1) increased the association of the targeted MOS and MSS with activated EC, although the targeted MOS showed a significantly higher VCAM-1 specific association than the targeted MSS. AbVCAM-1 MSS containing RelA siRNA achieved significant downregulation of RelA expression, while AbVCAM-1 MOS containing RelA siRNA did not downregulate RelA expression in activated EC. Additionally, AbVCAM-1 MSS containing RelA siRNA showed low cytotoxicity in EC and at the same time prohibited endothelial inflammatory activation by reducing expression of cell adhesion molecules. The AbVCAM-1 MSS formulation is a novel siRNA delivery system based on a combination of the cationic lipids MC3 and SAINT, that shows good physicochemical characteristics, enhanced endothelial cell association, improved transfection activity, low toxicity and significant anti-inflammatory effect, thereby complying with the requirements for future in vivo investigations.

Acknowledgements

The authors thank Timara Kuiper from the UMCG Endothelial Cell Facility for assisting in cell culturing. The authors thank Hans J. Kaper from the Dept. of Biomedical Engineering (UMCG, Groningen) for kindly providing assistance with zeta potential measurements.

Disclosure statement

No potential conflict of interest was reported by the author(s).

Data availability statement

Data are contained within this article.

Additional information

Funding

Y.H. gratefully acknowledges financial support from the China Scholarship Council [No. 201806240025].