Researchers at the University of Illinois at Chicago have demonstrated that magnetic nanoparticles can be used to ferry chemotherapy drugs into the spinal cord to treat hard-to-reach spinal tumours in an animal model. The unique delivery system represents a novel way to target chemotherapy drugs to spinal cancer cells, which are hard to reach because the drugs must cross the blood-brain barrier.
Spinal cord tumours are a challenge to treat because they are difficult to surgically remove due to their proximity to healthy spinal tissue and because chemotherapy drugs must cross the blood-brain barrier in order to reach them. Intramedullary spinal cord tumours account for 8 percent to 10 percent of all spinal cord tumours and are common among children and adolescents. Average survival for patients with these tumours is 15.5 months.
Doxorubicin, a commonly used chemotherapy to treat spinal tumours, is delivered intravenously and affects the whole body with poor penetration to the spine. Radiation therapy is also problematic for these tumours because the radiation often damages healthy nearby spinal tissue and can have devastating effects, including paraplegia.
“Getting chemotherapy drugs to spinal tumours has always been a problem,” said Dr. Ankit Mehta, assistant professor of neurosurgery and director of spinal oncology in the UIC College of Medicine and corresponding author on the paper. “But we can precisely guide chemotherapy to cancer cells into the spinal cord using magnetic nanoparticles.”
The researchers, whose results are published in the journal Scientific Reports, used a unique rat model with implanted human intramedullary spinal cord tumours to show that magnetic nanoparticles could successfully be used to kill tumour cells.
First, they created nanoparticles made up of tiny, metallic magnets bound to particles of doxorubicin. Next, they implanted a magnet just under the skin covering the spinal vertebrae in the rat models. Then they injected the magnetic nanoparticles into the space around the spinal cord where the tumour was located.
The magnet implanted in close proximity to the tumour guided the nanoparticles to the tumour sites. The researchers were able to show that tumour cells took up the nanoparticles and underwent apoptosis — in other words, they were effectively destroyed. The impact of the nanoparticles on nearby healthy cells was very minimal, Mehta said.
“This proof-of-concept study shows that magnetic nanoparticles are an effective way to deliver chemotherapy to an area of the body that has been difficult to reach with available treatments,” he said. “We will continue to investigate the potential of this therapy and hope to enter human trials if it continues to show promise.”
Pouyan Kheirkhan, Steven Denyer, Abhiraj Bhimani, Gregory Arnone, Darian Esfahani, Tania Aguilar, Jack Zakrzewski, Indu Venugopal, Nazia Habib, Andreas Linninger, and Dr. Fady Charbel of UIC, and Gary Gallia of Johns Hopkins University School of Medicine, are co-authors on the paper.
This research was supported in part by a Young Investigator Research Grant (G3895) from the AO Foundation, North America. Steven Denyer, a third-year medical student, was lead author on the study and receives research support from the Hispanic Center of Excellence at UIC.
Paper: Pouyan Kheirkhah, Steven Denyer, Abhiraj D. Bhimani, Gregory D. Arnone, Darian R. Esfahani, Tania Aguilar, Jack Zakrzewski, Indu Venugopal, Nazia Habib, Gary L. Gallia, Andreas Linninger, Fady T. Charbel, Ankit I. Mehta. Magnetic Drug Targeting: A Novel Treatment for Intramedullary Spinal Cord Tumors. Scientific Reports, 2018; 8 (1) DOI: 10.1038/s41598-018-29736-5