Trojan Horses: Nanoparticles sneak drugs into brain to battle cancer

Photo by dierk schaefer
Photo by dierk schaefer

I just read an interesting article in the Berkeley Science Review about using nanoparticles to make chemotherapy more effective against a type of brain cancer called glioblastoma. I was then surprised and proud when I realized one my former science-writing students, Dharsi Devendran, wrote it.

Although rare, glioblastoma is an invasive and deadly brain cancer with octopus-like tentacles that are difficult to completely remove with surgery. Even the standard combined treatment of surgery, radiation and chemotherapy isn’t very effective — people typically die within months of diagnosis. So researchers are actively searching for better treatments.

Devendran explains:

Although it is difficult to fight, glioblastoma also has a weakness. In its rush to feed itself, it accelerates the blood vessel formation process and creates hole-riddled blood vessels around the tumor. Because cancer drugs are small enough to slip through these holes, they can exploit this defect—but they also need a strategy to cross the blood-brain barrier in order to reach the tumor.

Acting like a security system for the brain, the blood-brain barrier is a network of blood vessels that allow essential nutrients to enter while blocking harmful molecules. Unfortunately, it also blocks life-saving chemotherapy drugs, unless researchers can find clever ways to sneak them through the barrier.

Ting Xu, PhD, professor of materials science at UC Berkeley, and her collaborators are developing tiny nanocarriers that can envelop and protect chemotherapy drugs as they move through the blood, across the blood-brain barrier, and into the brain to the glioblastoma tumor tissue.

The researchers designed a new nanocarrier, called a 3-helix micelle (3HM), out of proteins with molecules on the surface that fit into specific proteins found only on the surface of the tumor cells — like fitting a key into a lock. Once the 3HM nanocarriers access the tumor cells, they release their chemotherapy drugs to help destroy the glioblastoma.

Xu’s team has shown that their 3HM nanocarrier is twice as effective at reaching glioblastoma cells as liposomes, a nanocarrier made of fatty acids that is a standard in nanotechnology drug delivery. This is in part because the 3HM is five times smaller than liposomes.

“We still don’t understand the mechanism completely,” said JooChuan Ang, a graduate student in Xu’s group, in the article. “Size is definitely a factor, but there could be other factors that contribute…”

This is a reposting of my Scope blog story, courtesy of Stanford School of Medicine.

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Researchers develop molecular target for brain cancer

Images by Weibo Cai/Department of Radiology, University of Wisconsin-Madison. On the left, the antibody is linked to a label that shows up in a PET scanner, and the aggressive cancer shines brightly. On the right, a similar cancer without the molecular marker is less obvious.
Images by Weibo Cai/Department of Radiology, University of Wisconsin-Madison. On the left, the antibody is linked to a label that shows up in a PET scanner, and the aggressive cancer shines brightly. On the right, a similar cancer without the molecular marker is less obvious in the PET scan.

About 23,000 new cases of brain and central nervous system tumors are diagnosed annually, and more than 15,000 patients are expected to die of brain cancer this year in the United States, according to the American Cancer Society. Glioblastoma multiforme is the most common brain malignancy, but it remains incurable with only 5% of patients surviving at least 5 years after diagnosis. This bleak scenario has motivated the search for a better molecular target for glioblastoma multiforme diagnosis and therapy.

Weibo Cai, PhD, associate professor of radiology and medical physics, and his research team at the University of Wisconsin-Madison searched the Cancer Genome Atlas database and identified an effective biomarker for the deadly glioblastoma multiforme: the CD146 gene, which is highly active in glioblastoma.

CD146 genes place unique CD146 proteins on the surface of cells. Cai’s team developed an antibody that selectively latches onto the CD146 proteins concentrated on the glioblastoma tumors. They also tagged the antibody with a radioactive copper isotope, so the tumors could be easily identified and localized with a positron emission tomograph (PET), an imaging scanner commonly used to detect cancer.

Cai tested their antibody by implanting mice with human glioblastoma tumors, injecting them with the antibody and imaging them with a small animal PET scanner. The copper-labeled antibody preferentially accumulated in the tumors, allowing PET imaging to accurately identify tumors as small as 2 mm. Their study results were recently reported in the Proceedings of the National Academy of Sciences.

Cai explained in a university news release:

We’ve created a tag that – at least in our mouse model – is highly specific for this aggressive brain cancer. If the technique proves out in further tests, it could be used to diagnose some strains of aggressive glioblastoma, and also to evaluate treatment progress or even to test potential drugs.

The researchers also found high activity of CD146 in ovarian, liver, and lung tumors so their antibody could have a wide range of applications. However, there is a lot of research to be done before the technique could be used in the clinic. Cai said in the news release, “This targets tumors with the worst survival, but I want to emphasize that human trials are some years in the future.”

This is a reposting of my Scope blog story, courtesy of Stanford School of Medicine.