Rapidly Transducing and Spatially Localized Magnetofection Using Peptide-Mediated Non-Viral Gene Delivery Based on Iron Oxide Nanoparticles

Blokpoel Ferreras, Lia A.; Chan, Sze Yan; Vazquez Reina, Saul; Dixon, James E.

Abstract

Non-viral delivery systems are generally of low efficiency, which limits their use in gene therapy and editing applications. We previously developed a technology termed glycosaminoglycan (GAG)-binding enhanced transduction (GET) to efficiently deliver a variety of cargos intracellularly; our system employs GAG-binding peptides, which promote cell targeting, and cell penetrating peptides (CPPs), which enhance endocytotic cell internalization. Herein, we describe a further modification by combining gene delivery and magnetic targeting with the GET technology. We associated GET peptides, plasmid (p)DNA, and iron oxide superparamagnetic nanoparticles (MNPs), allowing rapid and targeted GET-mediated uptake by application of static magnetic fields in NIH3T3 cells. This produced effective transfection levels (significantly higher than the control) with seconds to minutes of exposure and localized gene delivery two orders of magnitude higher in targeted over non-targeted cell monolayers using magnetic fields (in 15 min exposure delivering GFP reporter pDNA). More importantly, high cell membrane targeting by GET-DNA and MNP co-complexes and magnetic fields allowed further enhancement to endocytotic uptake, meaning that the nucleic acid cargo was rapidly internalized beyond that of GET complexes alone (GET-DNA). Magnetofection by MNPs combined with GET-mediated delivery allows magnetic field-guided local transfection in vitro and could facilitate focused gene delivery for future regenerative and disease-targeted therapies in vivo.

Citation

Blokpoel Ferreras, L. A., Chan, S. Y., Vazquez Reina, S., & Dixon, J. E. (2021). Rapidly Transducing and Spatially Localized Magnetofection Using Peptide-Mediated Non-Viral Gene Delivery Based on Iron Oxide Nanoparticles. ACS Applied Nano Materials, 4(1), 167-181. https://doi.org/10.1021/acsanm.0c02465

• Journal Article Type: Article
• Acceptance Date: Dec 7, 2020
• Online Publication Date: Dec 21, 2020
• Publication Date: Jan 22, 2021
• Deposit Date: Dec 10, 2020
• Publicly Available Date: Dec 21, 2020
• Journal: ACS Applied Nano Materials
• Print ISSN: 2574-0970
• Electronic ISSN: 2574-0970
• Publisher: American Chemical Society
• Peer Reviewed: Peer Reviewed
• Volume: 4
• Issue: 1
• Pages: 167-181
• DOI: https://doi.org/10.1021/acsanm.0c02465
• Keywords: magnetofection, magnetic nanoparticles (MNPs), GAG-binding enhanced transduction (GET), cell penetrating peptide (CPP), magnetic targeting
• Public URL: https://nottingham-repository.worktribe.com/output/5131537
• Publisher URL: https://pubs.acs.org/doi/10.1021/acsanm.0c02465