Royal College of Surgeons in Ireland
pharmaceutics-12-01219-v2.pdf (6.97 MB)

Layered double hydroxide as a potent non-viral vector for nucleic acid delivery using gene-activated scaffolds for tissue regeneration applications

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journal contribution
posted on 2021-05-11, 15:46 authored by Lara Costard, Domhnall Kelly, Rachael Power, Christopher Hobbs, Sonia Jaskaniec, Valeria Nicolosi, Brenton CavanaghBrenton Cavanagh, Caroline CurtinCaroline Curtin, Fergal O'BrienFergal O'Brien
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.


Advanced scaffold-based therapeutics for regeneration of large volume, vascularised bone defects | Funder: Health Research Board (Ireland) | Grant ID: ILP-POR-2017-032

Center for Advanced Materials and Bioengineering Research (AMBER) (SFI/12/RC/2278 and SFI/12/RC/2278_P2)

Science Foundation Ireland (SFI) under the European Regional Development Fund under CÚRAM (13/RC/2073)

Irish Research Council Government of Ireland Postgraduate Program (GOIPG/2018/371)

European Research Council under the European Community’s Horizon 2020 Research and Innovation Program under ERC grant agreement no. 788,753 (ReCaP).



The original article is available at

Published Citation

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.

Publication Date

16 December 2020

PubMed ID



  • Amber (Advanced Material & Bioengineering Research) Centre
  • Anatomy and Regenerative Medicine
  • RCSI Tissue Engineering Group (TERG)

Research Area

  • Chemistry and Pharmaceutical Sciences
  • Cancer
  • Biomaterials and Regenerative Medicine
  • Immunity, Infection and Inflammation




  • Published Version (Version of Record)