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Nanotheranostics 2022; 6(3):306-321. doi:10.7150/ntno.68789 This issue Cite

Research Paper

Lanthanide-based β-Tricalcium Phosphate Upconversion Nanoparticles as an Effective Theranostic Nonviral Vectors for Image-Guided Gene Therapy

Flavia Rodrigues Oliveira Silva^1,2,3✉, Nelson Batista Lima¹, Maria Helena Bellini¹, Luiz Felipe Silva Teixeira¹, Eric Yiwei Du², Niloufar Jamshidi², Justin Gooding², Adam David Martin⁴, Alexander Macmillan⁵, Christopher Peter Marquis^3#✉, Pall Thordarson^2,6#✉

1. Instituto de Pesquisas Energéticas e Nucleares, São Paulo, 05508-000, Brazil
2. School of Chemistry, Faculty of Science, The University of New South Wales, Sydney NSW 2052, Australia
3. School of Biotechnology and Biomolecular Sciences, Faculty of Science, The University of New South Wales, Sydney NSW 2052, Australia
4. Dementia Research Centre, Department of Biomedical Sciences, Macquarie University, Sydney, NSW 2019, Australia
5. Katharina Gaus Light Microscopy Facility, Mark Wainwright Analytical Centre, Lowy Cancer Research Centre, The University of New South Wales, Sydney, NSW 2052, Australia
6. The UNSW RNA Institute, The University of New South Wales, Sydney NSW 2052, Australia
^# Authors contributed equally to this work

✉ Corresponding authors: Flavia Rodrigues Oliveira Silva, E-mail: frsilvabr; Christopher Peter Marquis, E-mail: c.marquisedu.au; Pall Thordarson, E-mail: p.thordarsonedu.au

Abstract

Lanthanide-based beta-tricalcium phosphate (β-TCP) upconversion nanoparticles are exploited as a non-viral vector for imaging guided-gene therapy by virtue of their unique optical properties and multi-modality imaging ability, high transfection efficiency, high biocompatibility, dispersibility, simplicity of synthesis and surface modification. Ytterbium and thulium-doped β-TCP nanoparticles (βTCPYbTm) are synthesized via co-precipitation method, coated with polyethylenimine (PEI) and functionalized with a nuclear-targeting peptide (TAT). Further, in vitro studies revealed that the nanotheranostic carriers are able to transfect cells with the plasmid eGFP at a high efficiency, with approximately 60% of total cells producing the fluorescent green protein. The optimized protocol developed comprises the most efficient βTCPYbTm/PEI configuration, the amount and the order of assembly of βTCPYbTm:PEI, TAT, plasmid DNA and the culturing conditions. With having excellent dispersibility and high chemical affinity toward nucleic acid, calcium ions released from βTCPYbTm:PEI nanoparticles can participate in delivering nucleic acids and other therapeutic molecules, overcoming the nuclear barriers and improving the transfection efficacy. Equally important, the feasibility of the upconversion multifunctional nanovector to serve as an effective contrast agent for imaging modality, capable of converting low-energy light to higher-energy photons via a multi-photons mechanism, endowing greater unique luminescent properties, was successfully demonstrated.

Keywords: lanthanide-based β-TCP, NIR upconversion theranostic nanoparticles, PEI, TAT, gene therapy.

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