An investigation of magnetic nanoparticle mediated methods for neuro-regeneration

Nahar, Tasmin Syeda

Abstract

Conditions such as Parkinsons disease, where specific cell types are affected such as the dopaminergic neurons in the substantia nigra pars compacta, cell transplantation and growth factor therapy could restore function and slow disease progression by introducing healthy cells. However previous attempts have had limited success due to the transplanted cells' inability to extend their axons over long distances and functionally integrate with the host cells. The ability to direct neurite growth and orientation over long distances have enormous implications for potential regenerative therapies.

Recent nanotechnology advancements have sparked interest in the therapeutic targeting of magnetic nanoparticles (MNPs) for neuro-regeneration. Previous research has demonstrated neurite outgrowth in single cells as well as the differentiation of neurons and neurite outgrowth via growth factors.

Despite these findings, they have been unable to stimulate long neurite outgrowth in a large number of cells. In this thesis, MNP approaches for neuro-regeneration are evaluated using brain-derived neurotrophic growth factor methods for neuron differentiation combined with magnetic force methods for neurite outgrowth via lysosomal uptake of MNPs.

It was possible to induce long-range orientation of neurites under magnetic force using lysosomal uptake of MNPs, as well as calculate forces as low as 10 fN per endosome required to induce orientation effects. In addition, a proteomic approach was used to elucidate biological mechanisms involved in neurite outgrowth under magnetic forces, yielding a number of proteins of interest that could be used for therapeutic targeting.

Finally, SH-SY5Y cells, a human neuroblastoma cell line which exhibit characteristics of immature neurons and are often used to investigate neuronal differentiation were used to assess BDNF-MNP conjugated cell differentiation. after 14 days of culture, BDNF conjugated to MNPs and uncoated commercial Micromod MNPs are shown to induce changes in the differentiation of the SH-SY5Y cells towards a neuronal phenotype.

These findings lay the groundwork for a better understanding of the biological mechanisms and forces that drive neurite outgrowth, as well as the ability to use MNPs as a biophysical cue for remote control of neurite outgrowth. As a result, it sheds light on the development of platforms and protocols for in vivo neuroregeneration and improved functional integration of neurons in cell therapies for neurodegenerative diseases.

Citation

Nahar, T. S. (2024). An investigation of magnetic nanoparticle mediated methods for neuro-regeneration. (Thesis). Keele University. Retrieved from https://keele-repository.worktribe.com/output/775525

• Thesis Type: Thesis
• Deposit Date: Mar 14, 2024
• Public URL: https://keele-repository.worktribe.com/output/775525
• Additional Information: Embargo on access until 1 January 2026 - The thesis is due for publication, or the author is actively seeking to publish this material.
• Award Date: 2024-03