Next Article in Journal
In Vivo Bactericidal Efficacy of GWH1 Antimicrobial Peptide Displayed on Protein Nanoparticles, a Potential Alternative to Antibiotics
Next Article in Special Issue
Novel PEGylated Lipid Nanoparticles Have a High Encapsulation Efficiency and Effectively Deliver MRTF-B siRNA in Conjunctival Fibroblasts
Previous Article in Journal
Mesoporous Silica Nanoparticles as a Potential Platform for Vaccine Development against Tuberculosis
Previous Article in Special Issue
Current Status and Challenges Associated with CNS-Targeted Gene Delivery across the BBB
 
 
Article

Layered Double Hydroxide as a Potent Non-viral Vector for Nucleic Acid Delivery Using Gene-Activated Scaffolds for Tissue Regeneration Applications

1
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
2
Centre for Research in Medical Devices (CÚRAM), Biomedical Sciences Building, National University of Ireland, Galway (NUI, Galway), H91 TK33 Galway, Ireland
3
Advanced Materials and Bioengineering Research Centre (AMBER), RCSI and Trinity College Dublin (TCD), College Green, D02 PN40 Dublin, Ireland
4
School of Chemistry and Centre for Research on Adaptive Nanostructures and Nanodevices (CRANN), Trinity College Dublin, College Green, D02 PN40 Dublin, Ireland
5
Cellular and Molecular Imaging Core, RCSI, 123 St Stephen’s Green, D02 YN77 Dublin, Ireland
6
Trinity Centre for BioMedical Engineering, Trinity Biomedical Sciences Institute, TCD, College Green, D02 PN40 Dublin, Ireland
*
Authors to whom correspondence should be addressed.
These authors contributed equally to this work.
Pharmaceutics 2020, 12(12), 1219; https://doi.org/10.3390/pharmaceutics12121219
Received: 11 November 2020 / Revised: 2 December 2020 / Accepted: 10 December 2020 / Published: 16 December 2020
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. View Full-Text
Keywords: biomaterials; scaffold; nonviral vector; gene therapy; layered double hydroxide; microRNA; siRNA; plasmid DNA; drug delivery biomaterials; scaffold; nonviral vector; gene therapy; layered double hydroxide; microRNA; siRNA; plasmid DNA; drug delivery
Show Figures

Graphical abstract

MDPI and ACS Style

Costard, L.S.; Kelly, D.C.; Power, R.N.; Hobbs, C.; Jaskaniec, S.; Nicolosi, V.; Cavanagh, B.L.; Curtin, C.M.; O’Brien, F.J. Layered Double Hydroxide as a Potent Non-viral Vector for Nucleic Acid Delivery Using Gene-Activated Scaffolds for Tissue Regeneration Applications. Pharmaceutics 2020, 12, 1219. https://doi.org/10.3390/pharmaceutics12121219

AMA Style

Costard LS, Kelly DC, Power RN, Hobbs C, Jaskaniec S, Nicolosi V, Cavanagh BL, Curtin CM, O’Brien FJ. Layered Double Hydroxide as a Potent Non-viral Vector for Nucleic Acid Delivery Using Gene-Activated Scaffolds for Tissue Regeneration Applications. Pharmaceutics. 2020; 12(12):1219. https://doi.org/10.3390/pharmaceutics12121219

Chicago/Turabian Style

Costard, Lara S., Domhnall C. Kelly, Rachael N. Power, Christopher Hobbs, Sonia Jaskaniec, Valeria Nicolosi, Brenton L. Cavanagh, Caroline M. Curtin, and Fergal J. O’Brien. 2020. "Layered Double Hydroxide as a Potent Non-viral Vector for Nucleic Acid Delivery Using Gene-Activated Scaffolds for Tissue Regeneration Applications" Pharmaceutics 12, no. 12: 1219. https://doi.org/10.3390/pharmaceutics12121219

Find Other Styles
Note that from the first issue of 2016, MDPI journals use article numbers instead of page numbers. See further details here.

Article Access Map by Country/Region

1
Back to TopTop