Diseases and Disorders

Combatting Alzheimer’s Disease Using Magnetic Fluorescent Nanoparticles

William Blair


Abstract

Alzheimer’s Disease is a neurological disorder that affects millions around the world, causing disabling progressive loss of memory and cognitive functions. While the effects of Alzheimer’s cannot be reversed with current medicine, there is hope to potentially slow down the effects. New forms of treatment for Alzheimer’s are now emerging in the experimental field of nanotechnology. These materials have increased magnetic and optical properties that help them act as an agent for early diagnoses. The nanoparticles are able to encapsulate molecules with therapeutic value while targeting specific transport processes in the brain vasculature. Specifically, superparamagnetic iron oxide nanoparticles (SPIONs) can bind to the amyloid plaques and become visible under MRI which have the ability to diagnose and treat Alzheimer’s Disease.

 

Alzheimer’s Disease

     Alzheimer’s Disease (AD) is the most common neurodegenerative disease in the world, characterized by progressive memory and cognitive dysfunction due to irreversible neuron degeneration [1]. The disease is caused by aggregations of extracellular amyloid plaques in the brain which are formed by interwoven β-amyloid fibrils. Since the plaques prevent neuronal signaling, AD eventually leads to total loss of autonomy and eventually to death.

     It currently affects nearly 30 million people worldwide, with a forecast of 60 million by 2050. There has been an 89% increase in deaths due to Alzheimer’s between 2000 and 2014. In America alone, the cost of Alzheimer’s also continues to rise, from $259 billion in 2017 to as much as $1.1 trillion by 2050, equivalent to a-third of Medicare dollars spent [1].
 

Treatment

    There is no cure for Alzheimer’s Disease and current medication can only temporarily slow the worsening of symptoms but only in the first stages of the disease. Established treatments provide only transitory symptomatic relief, temporarily improving cognitive function but do not slow the long- term progression of the disorder; early detection is thus of crucial importance. However, there is a theoretical treatment in the making that may serve to improve treatment effectiveness: nanoparticles. Nanoparticles are any particle less than 100 nanometers in size. Scientists have been developing unique nanoparticles that are meant specifically for drug delivery. These nanoparticles are so small that they can noninvasively penetrate most biological barriers and may even hold the potential to cross the blood brain barrier which prevents foreign substances from entering and causing trauma to the brain. This would yield a more effective diagnosis and treatment for Alzheimer’s patients [2].

    Several nanoparticles are currently being researched, however superparamagnetic iron oxide (Fe3O4) nanoparticles (SPIONs) are considered the most promising theranostic tool, capable of both diagnosing and treating the disease through the use of enhanced magnetic resonance imaging (MRI) [3]. The method is as follows:

  1. SPIONs are coated with silica molecules and Thioflavin-T (ThT), a non-toxic fluorescent dye that helps nanoparticles bind to amyloid beta plaques [4].

  2. These nanoparticles can then be immersed in a phosphate buffered saline solution and introduced into the body through femoral intravenous injection. Once injected, the nanoparticles are incubated for a period of 30 minutes.

  3. Following the incubation, the magnetic properties and fluorescent dye of the nanoparticles cause them to bind to aggregates of amyloid plaques in the brain                                                                                                                          

  4. Due to the metallic properties of nanoparticles, they are visible as small circular areas in MRI scans [5].

    This technology would allow doctors to diagnose Alzheimer’s disease beyond doubt for the first time because currently doctors cannot confidently diagnose Alzheimer’s until later stages of the disease, and cannot absolutely diagnose the disease until after the patient's death. Thus, this method offers the first absolute diagnostic tool for patients. This technology would allow Alzheimer’s to be diagnosed at an early stage because the aggregates are easily visible, allowing better treatment of the disease and better overall outcomes for patients.

    In addition to diagnostic ability, SPIONs also have the potential to inhibit amyloid beta-peptide formation because when an alternating current is applied to the brain, the magnetic properties of the nanoparticles cause the amyloid beta fibrils to separate, preventing the accumulation of amyloid plaques, thus lessening the effect of Alzheimer’s disease [5].

 

Applications

    SPIONs are attracting interest due to their abilities to carry drugs. These particles can be guided with an external magnetic field to the target and thus are able to deliver drugs effectively. Delivery of personalized medicine: Alzheimer’s drugs coupled with SPIONs to the target site is also a potential application of nanotechnology [8].

    There are many forms of nanotechnology available that can help in treating different types of diseases, whether it is cancerous tumors or neurodegenerative diseases.

    As researched and developed by Northwestern University, NanoFlare is a spherical nucleic acid with gold nanoparticle-enclosed DNA strands which can help detect breast cancer cells in the bloodstream. This can prevent metastasis and cancer cells forming a tumor [6].

    Nanoparticles also allow for the use of targeted medicine. When some nanoparticles are put to medicinal use, they can pass through the blood-brain barrier and deliver a specific drug to the brain.

     Due to the unfamiliarity with nanomedicine, scientists are still perfecting their design. The current developmental stage of nanoparticles has side effects such as bone marrow depression and a lower immune system [7]. Even though this may be discouraging, scientists are developing new structures of nanoparticles constantly and are closer to an optimal design as technology evolves.  

 

Conclusion

    Due to their high biocompatibility and superparamagnetic properties, SPIONs are valuable in diagnosing and treating Alzheimer’s. This is because they are capable of acting as a magnetic contrast agent and fluorescent dye for detection and also as an inhibitor for the aggregation of amyloid fibrils. SPIONs have far reaching applications beyond Alzheimer’s disease, in biotechnology, drug delivery and imaging. However, their novelty means that their side effects are unknown and further testing and development is needed to help patients use this technology.

    What is ultimately so amazing about SPIONs is that they are able to tackle the direct cause of Alzheimer’s unlike no method currently used. The use of these new therapeutic tools is bound to unleash a new era of possibility for patients currently suffering from extremely debilitating diseases without effective forms of treatment. It is clear that nanomedicine will lead the charge to that new paradigm.


References


  1. Fellman, Megan. (08/31/2018). Using Nanotechnology to Fight Cancer - Northwestern Now. Northwestern University. https://news.northwestern.edu/stories/2015/08/using-nanotechnology-to-fight-cancer. Retrieved June 25, 2018.

  2. Nanotechnology and Alzheimer disease. (n.d.) European Technology Platform. https://www.etp-nanomedicine.eu/public/about-nanomedicine/nanomedicine-applications/nanotechnology-and-alzheimer-disease. Retrieved June 29, 2018.

  3. Superparamagnetic iron-oxide nanoparticles (SPION)-enhanced MRI imaging. (11/06/2015). Retrieved from https://www.sepmag.eu/blog/superparamagnetic-iron-oxide-nanoparticles-spion-enhanced-mri-imaging. Retrieved June 29, 2018.

  4. Revia, Richard and Zhang, Miqin. (01/04/2016). Magnetite nanoparticles for cancer diagnosis, treatment, and treatment monitoring: Recent advances. Materials Today. https://www.sciencedirect.com/science/article/pii/S1369702115002734. Retrieved June 27, 2018.

  5. Tsolakis, A. C., Halevas, E., N. V., Koliakos, G. G., Salifoglou, A., & Litsardakis, G. (01/11/2017). Magnetic fluorescent nanoparticles binding to amyloid-beta peptide: Silica-coated, thioflavin-T functionalized iron oxide. IEEE Transactions on Magnetics. https://ieeexplore.ieee.org/document/7949148/. Retrieved June 26, 2018.

  6. Busquets, M. A., Sabaté, R., & Estelrich, J. (01/10/2014). Potential applications of magnetic particles to detect and treat Alzheimer's disease. Nanoscale Research Letters. https://nanoscalereslett.springeropen.com/articles/10.1186/1556-276X-9-538. Retrieved June 27, 2018.

  7. Leszek, Jerzy et al. (01/11/2017). Nanotechnology for Alzheimer’s Disease. Current Alzheimer Research. http://www.ingentaconnect.com/contentone/ben/car/2017/00000014/00000011/art00007. Retrieved June 25, 2018.

  8. Alzheimer's Statistics. (n.d.). Alzheimers.net. https://www.alzheimers.net/resources/alzheimers-statistics/. Retrieved June 26, 2018.

William Blair

William Blair


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