Nanoparticles Cross Blood-Brain Barrier Enabling "Brain Tumor Painting”

Researchers have been able to illuminate brain tumors by injecting into the bloodstream of mice fluorescent nanoparticles that safely cross the blood-brain barrier. The nanoparticles remained in mouse tumors for up to five days and did not show any evidence of damaging the blood-brain barrier.

Brain cancer is one of the most lethal of cancers. It is also one of the hardest to treat. Imaging results are frequently inexact because brain cancers are extremely invasive. Surgeons must saw through the skull and safely remove as much of the tumor as they can. Then doctors use radiation or chemotherapy to destroy cancerous cells in the surrounding tissue.

The study was conducted by researchers from the University of Washington (UW; Seattle, WA, USA) and published in the August 1, 2009, issue of the journal Cancer Research. The study's findings revealed that the nanoparticles improved the contrast in both magnetic resonance imaging (MRI) and optical imaging, which is used during surgery. "Brain cancers are very invasive, different from the other cancers. They will invade the surrounding tissue and there is no clear boundary between the tumor tissue and the normal brain tissue,” said lead author Dr. Miqin Zhang, a UW professor of materials science and engineering.

Being unable to differentiate a boundary complicates the surgery. 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.' The tumor will light up.”

Nanoimaging could also help with early cancer detection, according to Dr. Zhang. Current imaging techniques have a maximum resolution of 1 mm; nanoparticles could improve the resolution by a factor of 10 or more, allowing detection of smaller tumors and earlier treatment.

Until now, no nanoparticle used for imaging has been able to cross the blood-brain barrier and specifically bind to brain-tumor cells. With current techniques, clinicians inject dyes into the body and use drugs to temporarily open the blood-brain barrier, risking infection of the brain.

The UW team overcame this hurdle by constructing a nanoparticle that remains small in wet conditions. The particle was about 33 nm in diameter when wet, about one-third the size of similar particles used in other parts of the body.

Crossing the blood-brain barrier depends on the size of the particle, its lipid, or fat, content, and the electric charge on the particle. Dr. Zhang and colleagues built a particle that can pass through the barrier and reach tumors. To specifically target tumor cells they used chlorotoxin, a small peptide isolated from scorpion venom that many groups, including Dr. Zhang's, are examining for its tumor-targeting abilities. On the nanoparticle's surface Zhang placed a small fluorescent molecule for optical imaging, and binding sites that could be used for attaching other molecules.

Future research will evaluate this nanoparticle's potential for treating tumors, according to Dr. Zhang. She and colleagues already demonstrated that chlorotoxin combined with nanoparticles greatly slows tumors' metastasis. They will see whether that ability could extend to brain cancer, the most common solid tumor to affect children.

Merely improving imaging, however, would improve patient outcomes. "Precise imaging of brain tumors is phenomenally important. We know that patient survival for brain tumors is directly related to the amount of tumor that you can resect,” said coauthor Dr. Richard Ellenbogen, professor and chair of neurological surgery at the UW School of Medicine. "This is the next generation of cancer imaging,” he said. "The last generation was CT [computed tomography], this generation was MRI, and this is the next generation of advances.”

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