Novel Golden Lipid Nanoparticles with Small Interference Ribonucleic Acid for Substrate Reduction Therapy in Fabry Disease

Pharmaceutics. 2023 Jul 12;15(7):1936. doi: 10.3390/pharmaceutics15071936.

PMID: 37514122

Marina Beraza-Millor, Julen Rodríguez-Castejón, Jonatan Miranda

Highlights: The results of this study highlight the potential of the new siRNA-golden LNP system as a promising nanomedicine to address Fabry disease (FD) by specific SRT.

Abstract

Background: To stop the formation of globotriaosylceramide (Gb3), substrate reduction therapy (SRT) has been proposed as a novel gene therapy for Fabry disease (FD). Different siRNA targeted to Gb3 synthase (Gb3S) were included into nanomedicines.

Methods: The integration of various ligands, such as gold nanoparticles (GNs), protamine (P), and polysaccharides, as well as formulation parameters including composition and the method used to make solid lipid nanoparticles (SLNs) were assessed. In an FD cell type (IMFE-1), the novel siRNA-golden LNPs were successfully internalized, and GNs were detected in both the cytoplasm and the nucleus. The final composition and technique of production affected the silencing efficacy (measured by RT-qPCR), with silencing rates up to 90% (expressed as the reduction in Gb3S-mRNA). Higher system efficacy and stability were provided by GNs without compromising cell viability or hemocompatibility. With the most efficient formulations, immunocytochemistry experiments demonstrated Gb3S silencing for at least 15 days.

Conclusion: Overall, these findings demonstrate the new siRNA-golden LNP system's promise as an effective nanomedicine to address FD by specific SRT.

Keywords: Fabry disease, Gb3 synthase, gold nanoparticles, siRNA, solid lipid nanoparticles, substrate reduction therapy