Iron Oxide Nanoparticle-Mediated siRNA Delivery System for Huntington’s Disease Treatment
Sonali S. Rohiwal, T. D. Nguyen, Eva Kamenná, Jiřı́ Klı́ma, Michaela Vaškovičová, D. Sekac, Miroslav Šlouf, Ewa Pavlová, P. Stepanek, David Babuka, Hynek Beneš, Ognen Pop‐Georgievski, P. Ecorchard, Petr Bezdička, Darina Smržová, Knut Stieger, Zdeňka Ellederová
Abstract
Huntington’s disease (HD) is an autosomal dominant disease affecting neurons predominantly in the striatum due to the production of the toxic huntingtin protein. Lowering the concentration of mutant huntingtin is a promising therapeutic approach, and a suitable delivery system is fascinating. Nanoparticles (NPs) minimize the host immune response and have no limit concerning the number of NPs administered. They are safe, targeted, and effective for RNA therapeutics providing a significant mode to cross the blood–brain barrier for a broad range of clinical applications. The present study generated and characterized magnetic NPs (MNPs) using the co-precipitation method with a mean particle size of around 10–20 nm. The dynamic light scattering and zeta potential measurements showed that NPs exhibited narrow size distribution and sufficient colloidal stability. These oleic acid-coated MNPs were further cross-linked with polyethyleneimine and designed to deliver interfering RNA into human embryonic kidney cells (HEK-293) driven by an external magnetic field. These MNPs showed low cytotoxicity with high transfection efficiency. Furthermore, a transient downregulation was observed in endogenous huntingtin protein obtained by RT-PCR and Western blot analysis. Thus, these MNPs may represent a promising and efficient platform for siRNA delivery and provide a potential treatment strategy for HD.