Layered Double Hydroxide as a Potent Non-viral Vector for Nucleic Acid Delivery Using Gene-Activated Scaffolds for Tissue Regeneration Applications
Lara S. Costard,
Domhnall C. Kelly,
Rachael N. Power,
Christopher Hobbs,
Sonia Jaskaniec,
Valeria Nicolosi,
Brenton L. Cavanagh,
Caroline M. Curtin,
Fergal J. O’Brien
Affiliations
Lara S. Costard
Tissue Engineering Research Group, Department of Anatomy and Regenerative Medicine, Royal College of Surgeons in Ireland (RCSI), 123 St Stephen’s Green, D02 YN77 Dublin, Ireland
Domhnall C. Kelly
Tissue Engineering Research Group, Department of Anatomy and Regenerative Medicine, Royal College of Surgeons in Ireland (RCSI), 123 St Stephen’s Green, D02 YN77 Dublin, Ireland
Rachael N. Power
Tissue Engineering Research Group, Department of Anatomy and Regenerative Medicine, Royal College of Surgeons in Ireland (RCSI), 123 St Stephen’s Green, D02 YN77 Dublin, Ireland
Christopher Hobbs
Advanced Materials and Bioengineering Research Centre (AMBER), RCSI and Trinity College Dublin (TCD), College Green, D02 PN40 Dublin, Ireland
Sonia Jaskaniec
Advanced Materials and Bioengineering Research Centre (AMBER), RCSI and Trinity College Dublin (TCD), College Green, D02 PN40 Dublin, Ireland
Valeria Nicolosi
Advanced Materials and Bioengineering Research Centre (AMBER), RCSI and Trinity College Dublin (TCD), College Green, D02 PN40 Dublin, Ireland
Brenton L. Cavanagh
Cellular and Molecular Imaging Core, RCSI, 123 St Stephen’s Green, D02 YN77 Dublin, Ireland
Caroline M. Curtin
Tissue Engineering Research Group, Department of Anatomy and Regenerative Medicine, Royal College of Surgeons in Ireland (RCSI), 123 St Stephen’s Green, D02 YN77 Dublin, Ireland
Fergal J. O’Brien
Tissue Engineering Research Group, Department of Anatomy and Regenerative Medicine, Royal College of Surgeons in Ireland (RCSI), 123 St Stephen’s Green, D02 YN77 Dublin, Ireland
Nonviral vectors offer a safe alternative to viral vectors for gene therapy applications, albeit typically exhibiting lower transfection efficiencies. As a result, there remains a significant need for the development of a nonviral delivery system with low cytotoxicity and high transfection efficacy as a tool for safe and transient gene delivery. This study assesses MgAl-NO3 layered double hydroxide (LDH) as a nonviral vector to deliver nucleic acids (pDNA, miRNA and siRNA) to mesenchymal stromal cells (MSCs) in 2D culture and using a 3D tissue engineering scaffold approach. Nanoparticles were formulated by complexing LDH with pDNA, microRNA (miRNA) mimics and inhibitors, and siRNA at varying mass ratios of LDH:nucleic acid. In 2D monolayer, pDNA delivery demonstrated significant cytotoxicity issues, and low cellular transfection was deemed to be a result of the poor physicochemical properties of the LDH–pDNA nanoparticles. However, the lower mass ratios required to successfully complex with miRNA and siRNA cargo allowed for efficient delivery to MSCs. Furthermore, incorporation of LDH–miRNA nanoparticles into collagen-nanohydroxyapatite scaffolds resulted in successful overexpression of miRNA in MSCs, demonstrating the development of an efficacious miRNA delivery platform for gene therapy applications in regenerative medicine.
