The fight against cancer is an all-hands-on-deck battle.
UCF researcher Sudipta Seal joined the fight by collaborating with Johns Hopkins Kimmel Cancer Center to provide a key component for a targeted medicine that combats the most common kind of pediatric brain tumor.
Seal, who is a professor and Chair of the Materials Science and Engineering Department within the College of Engineering and Computer Science, along with his postdoctoral researcher Elayaraja Kolanthai, created a solution containing therapeutic cerium oxide nanoparticles that acts as a protective vehicle to deliver a combination of cancer therapies through the body and to a patient’s brain. Their work was recently published in the journal Cell Reports.
A Targeted Approach
The intravenous mixture of therapies attacks medulloblastomas – or tumors – on all fronts. Ranjan Perera, director of the Center for RNA Biology at Johns Hopkins All Children’s Hospital in St. Petersburg, Florida, and his team developed the medicine that targets a specific part of RNA that “reprograms” a region of our DNA to hinder cancer causing genes.
A specific, long non-coding RNA, lncRNA, was identified as a potential bullseye target that accumulates and promotes cancerous growth. Johns Hopkins assembled a sequence of nucleotides – the building blocks of RNA – that can bind to the specific parts of the cancer-promoting portion of the RNA and destroy it.
Perera and his team paired the genetic treatment with cisplatin, a common intravenous chemotherapy medication that disrupts cancer cells and prevents them from replication.
The treatment was tested in mice and results showed that it inhibits tumor growth by 40-50%. The intravenous method may have an advantage as an alternative therapy to craniospinal irradiation as it may have less long-term side effects and risk of relapse.
The hope is once this specific genetic expression is identified and this treatment is administered, the malignant tumor growth can be halted and even eliminated in human patients.
Safe Delivery
Protecting the combination of promising treatments, bolstering therapeutic value and ensuring they reach their target is precisely what the cerium oxide was intended to do, Seal says.
“We can attach various drugs to the nanoparticles and deliver them to a specific site for medical intervention,” he says. “The medication on its own already has its own applications, so when you combine them, their role in intervention becomes quite significant. We are quite excited about this.”
Seal and Perera previously had worked together and were familiar with each other’s work. After a few conversations between the two, a collaboration on this pediatric cancer research seemed like a good fit.
“This medication can be very difficult to deliver to sites,” Seal says. “Dr. Perera and I knew each other and so there was mutual interest between us both. I spoke with Dr. Perera, and he said that he had microorganisms to deliver, and that we’ve been studying oxides for a long time. They’re very well known in medicine, and here we are at UCF we’re well known for our oxide vector delivery.”
Seal’s cerium oxide has been used in a variety of biomedical and therapeutic applications even before it was used in the Johns Hopkins study. The cerium oxide nanoparticles previously were shown to aid in healing diabetic wounds and to maintain bone strength during cancer treatments.
What makes these specific nanoparticles so useful is that because they are oxides, they can bond with such a varied spectrum of other compounds at the molecular level, Seal says.
“Oxides are omnipresent in nature, and so they can be fairly compatible with many things,” he says. “It’s almost like a LEGO block. You’ve got many anchors to attach to on it and many different kinds to attach to.”
For this instance, the cerium oxide ensures the genetic therapy and chemotherapy successfully travels to the site of the brain tumor rather than taking any pit stops along the way, Seal says.
“It has the power to be like a GPS system,” he says. “You can program it to go to a specific address, or maybe it’ll make a stop or bypass a stop. That is the power of what we can do with nanotechnology.”
Studying and tweaking the particles (which are less than 10 nanometers in length) in water allows them to be highly customizable and to fit like a block or travel to the correct site.
Seal is greatly encouraged by the promise of the study and is excited to continue pursuing other ways to utilize his cerium oxide.
He invites other researchers to collaborate and see if he and his nanoparticles make a good fit.
“We’re open to opportunities,” Seal says. “I think this nano oxide vector can really help, and it opens a whole door of other biomedical opportunities that needs to be explored. We can modulate our nano vector in a way that it can sense and intervene in many ways. We’re happy to see if any other drugs can be attached to our molecules.
The research was funded by the National Institutes of Health, National Cancer Institute and various other sources.
The researchers plan to study the therapy in humans to further test its safety and efficacy in hopes of triumphing over pediatric cancer and providing relief for children with cancer.
Researcher’s Credentials:
Seal joined UCF’s Department of Materials Science and Engineering and the Advanced Materials Processing Analysis Center, which is part of UCF’s College of Engineering and Computer Science, in 1997. He has an appointment at the College of Medicine and is a member of UCF’s Biionix faculty cluster initiative. He is the former director of UCF’s NanoScience Technology Center and Advanced Materials Processing Analysis Center. He received his doctorate in materials engineering with a minor in biochemistry from the University of Wisconsin and was a postdoctoral fellow at the Lawrence Berkeley National Laboratory at the University of California Berkeley.