Research Article

Poly-L-lysine as a crosslinker in bile acid and alginate nanoaggregates for gene delivery in auditory cells

The Biotechnology & Drug Development Research Laboratory, Curtin Medical School & Curtin Health Innovation Research Institute, Curtin University, Bentley 6102, Perth, Western Australia, Australia

Department of Clinical Biochemistry, Pathwest Laboratory Medicine, Royal Perth Hospital, Perth 6000, Western Australia, Australia

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Corina Mihaela Ionescu

https://orcid.org/0000-0002-8966-0448

The Biotechnology & Drug Development Research Laboratory, Curtin Medical School & Curtin Health Innovation Research Institute, Curtin University, Bentley 6102, Perth, Western Australia, Australia

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Melissa Jones

The Biotechnology & Drug Development Research Laboratory, Curtin Medical School & Curtin Health Innovation Research Institute, Curtin University, Bentley 6102, Perth, Western Australia, Australia

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Susbin Raj Wagle

https://orcid.org/0000-0001-9867-8896

The Biotechnology & Drug Development Research Laboratory, Curtin Medical School & Curtin Health Innovation Research Institute, Curtin University, Bentley 6102, Perth, Western Australia, Australia

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Bozica Kovacevic

https://orcid.org/0000-0002-9359-7840

The Biotechnology & Drug Development Research Laboratory, Curtin Medical School & Curtin Health Innovation Research Institute, Curtin University, Bentley 6102, Perth, Western Australia, Australia

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Patrick Lim

The Biotechnology & Drug Development Research Laboratory, Curtin Medical School & Curtin Health Innovation Research Institute, Curtin University, Bentley 6102, Perth, Western Australia, Australia

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Armin Mooranian

*Author for correspondence: Tel.: +61 892 661 318;

E-mail Address: a.mooranian@curtin.edu.au

https://orcid.org/0000-0001-7103-2067

The Biotechnology & Drug Development Research Laboratory, Curtin Medical School & Curtin Health Innovation Research Institute, Curtin University, Bentley 6102, Perth, Western Australia, Australia

School of Pharmacy, University of Otago, Dunedin, Otago 9016, New Zealand

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Hani Al-Salami

**Author for correspondence: Tel.: +61 892 669 816;

E-mail Address: hani.al-salami@curtin.edu.au

https://orcid.org/0000-0003-0049-6969

The Biotechnology & Drug Development Research Laboratory, Curtin Medical School & Curtin Health Innovation Research Institute, Curtin University, Bentley 6102, Perth, Western Australia, Australia

Medical School, University of Western Australia, Perth 6000, Western Australia, Australia

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Published Online:4 Sep 2023https://doi.org/10.2217/nnm-2023-0152

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Abstract

Background: Hearing loss is a condition that may affect a wide array of patients from various backgrounds. There are no cures for sensorineural hearing loss. Gene therapy is one possible method of improving hearing status; however, gene delivery remains challenging. Materials & methods: Polymer nanoaggregates of alginate and poly-L-lysine were prepared with and without bile acid. The nanoaggregates had physical properties, cytotoxicity, gene release and gene expression analyzed. Results & discussion: The nanoparticles produced had appropriate size and charge, low cytotoxicity between 0.5 and 1.0 mg/ml and linear gene release but poor transfection efficiency. Conclusion: The present study provides preliminary evidence for the efficacy of polymer nanotechnology with bile acids for inner ear gene delivery; optimization is required to improve transfection efficiency.

Plain language summary

Hearing loss is a global issue with significant consequences. Gene therapy is an emerging technique in the management of various conditions, including hearing loss. This involves the delivery of a new copy of a gene to a cell with a missing or defective copy of that gene. The delivery of genes such as ATOH1 has been shown to encourage cell differentiation into new functional hair cells to potentially reverse hearing loss. Unfortunately, effective and safe delivery of genes remains challenging. Polymer nanoparticles represent one method for delivering genes that allows for customizability in size, structure and function. In this study, the authors developed nanoparticles with a polymer derived from algae called alginate, an amino acid polymer called poly-L-lysine and bile acid to improve gene delivery to inner ear cells. A cell line derived from the inner ear of a mouse was used to test the effectiveness of these particles at delivering genes. A gene that makes cells that uptake these particles fluoresce was included in the nanoparticles, to demonstrate they are capable of gene delivery. In the future, this gene could be replaced with genes associated with encouraging cell differentiation. The preliminary results of this study suggest that such nanoparticles may be capable of gene delivery, although further optimization is required.

Keywords:

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Vol. 18, No. 19

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History

Received 26 May 2023

Accepted 14 August 2023

Published online 4 September 2023

Published in print August 2023

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Acknowledgments

The authors acknowledge the Australian Research Training Program (RTP) Scholarship for their support. The authors also acknowledge the use of laboratory equipment and the scientific and technical assistance of the Curtin University Electron Microscope Facility, which has been partially funded by the university, state and commonwealth governments. The authors are also very grateful to Young Joon Seo (Yonsei University Wonju College of Medicine) and Federico Kalinec (University of California, CA, USA) for the auditory cell line used in this study.

Financial & competing interests disclosure

This work is partially supported by the European Union Horizon 2020 research project and innovation program under the Marie Skłodowska-Curie Grant Agreement no. 872370. This work is also supported partially by Curtin Faculty ORS-WAHAI Consortium, the Australian National Health and Medical Research (APP9000597). The authors have no other relevant affiliations or financial involvement with any organization or entity with a financial interest in or financial conflict with the subject matter or materials discussed in the manuscript apart from those disclosed.

No writing assistance was utilized in the production of this manuscript.

Availability of data & materials

The datasets generated and/or analyzed during the current study are not publicly available but are available from the corresponding author on reasonable request due to pending commercialization limitation.

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