The Role of Nanotechnology and Nanoparticles in the Treatment of Brain Tumors

Cancer is a prominent topic in the medical field and in everyday life. It is not uncommon to find someone who knows or knew someone with cancer. Cancer also happens to remain one of the most challenging medical disorders in humans with very large implications on socioeconomics in all levels of society. Basic and clinical research as well as treatment are generally handled by specialized practitioners and scientists who attempt to overcome the obstacles that are innate to these diseases. There are a variety of cancers that affect different parts/systems and organs in the human body. At present, the most common approaches to treating cancers include surgery, radiation, and chemotherapy, all of which potentially cause significant side effects/complications and are a great burden on financial resources. However, recent advances in medical understanding and technology such as nanotechnology show a lot of promise in treating cancers such as brain cancers or tumors. Medical researchers such as Alexander Stegh, PhD, a professor of Neurology in the Division of Neuro-oncology and of Medicine, and Chad Mirkin, PhD, (Professor of Chemistry/Professor of Medicine in the Division of Hematology and Oncology and Director of the International Institute for Nanotechnology) at Northwestern University for example, have been conducting research utilizing nanotechnology in the form of nanoparticles in conjunction with spherical nucleic acids in the treatment of a type of brain cancer called a glioblastoma (Williams, 2017).

Glioblastomas are a particularly deadly form of brain cancer that are known to be aggressive and difficult to detect. They operate by sending out microscopic roots that reach deep into brain tissue, but surgical removal is a possible treatment if the tumor is above the eye, with the possibility of relative sparing of damage to brain functions. Following surgery are rounds of radiation and chemotherapy. However, even in those individuals who respond to treatments, the glioblastoma can return within a year or two. Ultimately, glioblastomas can kill those afflicted by interfering with bodily functions. This type of cancer is pretty uncommon, but some well known individuals have been affected by it such as senator John McCain of Arizona (a survivor), the former film critic Gene Siskel, and former senator Edward M. Kennedy of Massachusetts (Sun-Times Staff, 2017).

          Given the relative lack of effective treatment options for a number of diseases, nanotechnology in recent years has been starting to make some headway into contributing to the treatment of a variety of medical conditions including cancers such as the glioblastoma. A clinical trial is in the early-stages at Robert H. Lurie Comprehensive Cancer Center of Northwestern University (Northwestern Medicine) that shows promise in tackling glioblastoma. Alexander Stegh, PhD, has been working in collaboration with Chad Mirkin, PhD, to develop a novel drug candidate currently referred to as NU-0129 that is capable of traversing the blood-brain barrier and targets a gene (identified by Alexander Stegh and colleagues) called BCL2L12 that plays a role in programmed cell death (also known as apoptosis). The composition of this drug consists of spherical nucleic acids (bits of RNA that also happen to be nanostructures themselves) that have been attached onto spherical gold nanoparticles (which are only 13 nanometers in diameter). This approach, which was created by Chad Mirkin in 1996, is unique because it can serve as a platform for the targeting of pathways that are involved in certain neurological disorders like Alzheimer’s and Parkinson’s by reducing activity of the genes that lead to their onset. While effectiveness has been demonstrated in lab mice via intravenous injection, switching the gene responsible for onset of glioblastoma off (significant reduction in tumor size and progression as well as somewhat increased survivability), researchers want to know whether the drug can cross the blood-brain barrier in humans and exert the same beneficial effects. The most fascinating thing about this wonderful development is that it is the first time that anyone realized that nanostructures were capable of being injected into animals and also be able to find their way to the brain while providing therapeutic effects (Paul and Fellman, 2017).

At present, the clinical trial with humans is being conducted by lead investigator Dr. Priya Kumthekar, an assistant professor of neurology and hematology-oncology at Feinberg School of Medicine/neuro-oncologist at Northwestern Medicine. The study intends to recruit up to 8 glioblastoma patients whose tumors have recurred and are suitable candidates for surgical removal. The procedure involves administering the drug intravenously before surgery and after removal of the tumor, Dr. Kumthekar’s team will assess how much of the drug accumulated in the brain tumor tissue and how effective the blood-brain barrier penetration was (Paul and Fellman, 2017). All these efforts clearly demonstrate just how multi/interdisciplinary neuroscience really is. One can see this by taking note of the collaborative efforts of medical/scientific professionals and researchers from separate scientific fields to discover, innovate, and create newer, more effective treatments and techniques for the most complex and challenging health problems in human society. If the clinical trial of drug candidate NU-0129 proves successful, it may result in significant time and cost savings as well as decreased suffering of patients in the form of increased survival rates and less medical complications from the standard cancer treatment modalities. Fruitful results from these collaborative efforts would also prove the worthiness of nanotechnology and nanomedicine’s role in neuroscience and medicine. It is most astonishing that all these efforts from preclinical research through clinical trials are being done in-house at Northwestern University without the involvement (funding) of an outside party such as a pharmaceutical company or the government, in contrast to a well-known previous collaboration with Pfizer on the development of the anti-convulsant/epilepsy drug Lyrica (pregabalin), which was discovered and synthesized by Richard Bruce Silverman, PhD, a medicinal chemist from Northwestern University. This is another way that nanoparticles can be utilized in medicine other than the lovastatin-encapsulated poly(lactic-co-glycolic) acid (PLGA) nanoparticles that Evan B. Stubbs, Jr., PhD, of the Loyola University Medical Center (Department of Ophthalmology), used to attenuate experimental autoimmune neuritis in mice as a model of Guillain–Barré syndrome (an autoimmune disease that damages the peripheral nervous system) and presented during his talk at Loyola University Chicago on November 7, 2017 (Stubbs, Jr., 2017). 

References

Paul, Marla, and Megan Fellman. “First spherical nucleic acid drug injected into humans targets brain cancer.” Northwestern: Northwestern Now, 11 May 2017, https://news.northwestern.edu/stories/2017/may/spherical-nucleic-acid-drug-human-brain-cancer-glioblastoma/. Accessed 10 December 2017.

“Prized Science - Chad Mirkin: Gold Nanoparticles & The Future of Medical Diagnostics.” Youtube, uploaded by BytesizeScience, 22 August 2012. https://www.youtube.com/watch?v=_MgMiK7LKc8. Accessed 11 December 2017.

Staff Author. “Brain cancer McCain has killed Gene Siskel, Tim Weigel, Ted Kennedy.” Chicago Sun-Times, 20 July 2017, https://chicago.suntimes.com/chicago-politics/brain-cancer-afflicting-mccain-also-killed-gene-siskel-tim-weigel/. Accessed 10 December 2017.

Stubbs, Jr., Evan B. “Targeting the Blood-Nerve Barrier for the Management of Inflammatory Peripheral Neuropathies.” 7 November 2017. Loyola University Chicago, Chicago, IL. Speaker Presentation.

“Targeting a rare, fatal brain cancer with spherical nucleic acids.” Youtube, uploaded by NorthwesternU, 11 May 2017. https://www.youtube.com/watch?v=rey_IGslteA. Accessed 10 December 2017.

Williams, Anna. “Making a Mark in Translational Medicine.” Northwestern Medicine: Feinberg School of Medicine News Center, 22 August 2017, http://news.feinberg.northwestern.edu/2017/08/making-a-mark-in-translational-medicine/. Accessed 10 December 2017.