Nanoparticles Cross Blood-Brain Barrier To Enable “Brain Tumor Painting”
Earlier this year, researchers at the University of Washington reported that they had developed a toxin-nanoparticle combination that inhibits brain cancer invasion (click here for story) when added to tumor cells growing in culture. Now, the same group of investigators, led by Miqin Zhang, Ph.D., principal investigator of the Nanotechnology Platform for Pediatric Brain Cancer Imaging and Therapy, has developed an improved version of this toxin-nanoparticle construct that, when injected into animals, can cross the blood-brain barrier (BBB) and reveal the presence of tumors in the brain.
This new nanoparticle agent, which Dr. Zhang and her colleagues describe in the journal Cancer Research, is made up of an iron oxide nanoparticle coated with a biocompatible polymer that enables the nanoparticle to breach the normally impermeable layer of cells that separates the brain’s blood supply from the rest of the body (the BBB). To target brain tumors, the researchers attached chlorotoxin, a component of scorpion venom that has a remarkable affinity for tumor cells. They also attached a fluorescent molecule as a second imaging agent; the nanoparticle itself effectively boosts magnetic resonance imaging (MRI) signals. Test results showed that the nanoparticles improved the contrast in both MRI and optical imaging, which is used during surgery to pinpoint a tumor’s location in the surgical field.
“Brain cancers are very invasive, different from other cancers. They will invade the surrounding tissue, and there is no clear boundary between the tumor tissue and the normal brain tissue,” said Dr. Zhang. The inability to distinguish a boundary complicates surgery, and severe cognitive problems are a common side effect.
“If we can inject these nanoparticles with infrared dye, they will increase the contrast between the tumor tissue and the normal tissue,” Dr. Zhang said. “So during the surgery, the surgeons can see the boundary more precisely. We call it brain tumor illumination or brain tumor painting.”
This work, which is detailed in the paper “Specific targeting of brain tumors with an optical/magnetic resonance imaging nanoprobe across the blood-brain barrier,” was supported by the NCI Alliance for Nanotechnology in Cancer, a comprehensive initiative designed to accelerate the application of nanotechnology to the prevention, diagnosis, and treatment of cancer. Investigators from the Fred Hutchinson Cancer Research Center and the Seattle Children’s Hospital and Regional Medical Center also participated in this study. An abstract is available at the journal’s Web site.