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

Thomas Foster, Corina Mihaela Ionescu, Melissa Jones, Susbin Raj Wagle, Bozica Kovacevic, Patrick Lim, Armin Mooranian, Hani Al-Salami

Research output: Contribution to journalArticlepeer-review

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.

Original languageEnglish
Pages (from-to)1247-1260
Number of pages14
JournalNanomedicine
Volume18
Issue number19
DOIs
Publication statusPublished - 1 Aug 2023

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