Interdisciplinary Innovations: Engineering Solutions Against Cancer


By Arushi Atluri | UTS Staff Writer | SQ Online (2014-15)

 

As both students and professional researchers make their journeys along the path of biology, they often become immersed in solutions and innovations based within their field. It is natural to want to stroll along a straightforward, familiar route within one’s own niche; one might even wonder how information from other fields, such as visual arts, structural engineering, or psychology, could solve biological problems like AIDS. With his nanoengineering-based research and breakthrough technology regarding cancer cells, however, Dr. Inanc Ortac shows the importance of an interdisciplinary method for solving some of biology’s loftiest questions.

About Dr. Ortac and the Problem

Dr. Ortac earned his bachelor’s degree in physics at the Middle East Technical University, received a PhD in electrical engineering at UC San Diego, and did research in a UCSD nanoengineering professor’s lab — three fields that one may think do not necessarily directly connect with cancer. However, Dr. Ortac is “particularly interested in biomedical applications [of his skills], since the need for solutions is most urgent and solutions have a tremendous impact directly on people’s lives” and has “always seen [himself] as an engineer who finds solutions to problems that we face in our lives.”

As many are familiar with, cancer is a disease characterized by abnormal, infinitely dividing cells that invade tissues in the body and  create tumors that are sometimes fatal. So far, there is no universal, infallible cure for this illness; however, treatments like chemotherapy have been used to control cancer cell growth. Researchers have also found that a foreign enzyme derived from nonhuman organisms, such as E. coli, can be used to starve cancer cells during chemotherapy, decreasing the time patients must spend going through the uncomfortable side effects of chemotherapy. The specific enzyme is asparaginase, and it reacts with the amino acids specifically necessary for cancer cells to survive, thereby “starving” them. However, one problem with asparaginase is that, since the enzyme is not derived from the human body, the immune system ultimately destroys the enzyme.

SHELS as a Solution

As part of his research at UCSD, Dr. Ortac developed the platform technology to prevent the destruction of asparaginase. The solution was to encapsulate the enzyme in a “shell” to shield it from the immune system. Fabricated with silica, the shell is designed as a nanoporous material with a mesoporous interior. The enzymes are first loaded into the larger mesopores. Then, these mesopores are sealed with the nanoporous material to finally create the “synthetic hollow enzyme loaded nanospheres,” or SHELS for short. Small molecules, like amino acids, are able to diffuse through the nanoporous shell, while larger molecules, like enzymes, are unable to escape the shell; therefore, the enzyme remains trapped in the sphere, while amino acids are still able to diffuse in and out for the enzyme to use. Since the shells are made of silica, they have low toxicity, are biocompatible, have adjustable porosity, and, most importantly, are biodegradable; therefore, they reside in the body for just about two months. Dr. Ortac states, “Nanomaterials are at the interface of the molecular and macro worlds, [and] manipulation of molecular interactions requires materials engineered in the nanoscale.  We manipulate the physical and surface properties of the nanoparticles…depending on the application we are aiming for…[and] these modifications at the nanoscale give us the opportunity to address problems in a more complete way, which was missing in old generation therapeutic approaches.”

SHMS-and-SHELS

Figure 1: Scanning electron micrograph of the loaded SHELS. Enzymes (green) are encapsulated within the large-holed, mesoporous  inner shell (dark grey) and small-holed, nanoporous outer shell (light grey) and protected from the body’s antibodies

Future Outlook for SHELS

Currently, Dr. Ortac is the Chief Technology Officer at DevaCell Inc., a company he helped found. DevaCell’s purpose is to translate his developed nanotechnology platform to the clinic, and the company already has a lab and licensed patents from UCSD to start developing SHELS further. The technology will be used not only in oncology, but also for refractory gout diagnostics and sensing, where gout is a form of arthritis caused by the buildup of uric acid deposits in the body. “We are in the preclinical stage doing animal studies, and plan to start human clinical trials in a few years,” responds Dr. Ortac, “[Although] clinical trials will be a whole different experience…we are hopeful for success.” In conclusion, even though more research still has to be done on the medical application of SHELS, future utilizations of the encapsulating shell and more engineering solutions to fight cancer are on the horizon.

The Importance of Thinking Outside and Beyond the Box

The fabrication of SHELS is just the beginning not only for Dr. Ortac and his colleagues at DevaCell, but also for the rise of interdisciplinary solutions to complex biological problems relating to the general population. As the door to more prospective cancer therapeutics involving nanoengineering opens, so do more doors leading researchers in other fields to help battle the physical and emotional toll cancer takes on its victims and their loved ones. The main road to a cure for cancer is definitely a long, twisted and uncertain one; by embracing interdisciplinary perspectives and innovations, though, researchers may soon find alternative shortcuts to the final destination. “Diseases like cancer have proven to be way more complicated than it was once thought,” says Dr. Ortac. “Therefore, a broad scope and ability to look at issues from different perspectives allows us to comprehend the big picture and brings us closer to the solution. At this moment, for researchers, expanding out of their specific field of study has become a necessity.”


References:

Ortac, Inanc et al. “Dual-Porosity Hollow Nanoparticles for the Immunoprotection and Delivery of Nonhuman Enzymes.” Nano Letters. N.p., 28 Jan. 2014. Web. 16 Jul. 2014.

http://www.tsienlab.ucsd.edu/Publications/Ortac%202014%20Nano%20Letters%20-%20Dual-Porosity%20Hollow%20Nanoparticles.pdf

Hockmuth, Catherine. “Nanoshell Shields Foreign Enzymes Used to Starve Cancer Cells from Immune System.” UC San Diego News Center. N.p. 17 Jun. 2014. Web. 16 Jul. 2014.

http://ucsdnews.ucsd.edu/pressrelease/nanoshell_shields_foreign_enzymes_used_to_starve_cancer_cells_from_immune_s

“Defining Cancer.” National Cancer Institute. N.p. 7 Mar. 2014. Web. 16 Jul. 2014.

http://www.cancer.gov/cancertopics/cancerlibrary/what-is-cancer

“Questions and Answers About Chemotherapy.” National Cancer Institute. N.p. 29 Jun. 2007. Web. 16 Jul. 2014.

http://www.cancer.gov/cancertopics/coping/chemotherapy-and-you/page2

http://devacell.com/

“Nanoshell shields foreign enzymes used to starve cancer cells from immune system.” Kurzwell Accelerating Intelligence. N.p. 3 Jul. 2014. Web. 16 Jul. 2014. [FOR THE IMAGES]

http://www.kurzweilai.net/nanoshell-shields-foreign-enzymes-used-to-starve-cancer-cells-from-immune-system?utm_source=KurzweilAI+Weekly+Newsletter&utm_campaign=60131025df-UA-946742-1&utm_medium=email&utm_term=0_147a5a48c1-60131025df-282129417


About

My name is Arushi Atluri and I am a second year General Biology major from Muir College. I'm currently a staff writer for Under the Scope, Saltman Quarterly's sister publication; writing is one of my passions, so it’s great to be able to apply it to biology and research! Some of my other hobbies include swimming, eating weird foods, going to the beach, watching football (go Niners!), and volunteering.