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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 11.05.2021, 15:46 by Lara Costard, Domhnall Kelly, Rachael Power, Christopher Hobbs, Sonia Jaskaniec, Valeria Nicolosi, Brenton Cavanagh, Caroline Curtin, Fergal 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.

Funding

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).

History

Comments

The original article is available at https://www.mdpi.com

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

33339452

Department/Unit

  • 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

Publisher

MDPI AG

Version

  • Published Version (Version of Record)