Scorpion Venom with Nanoparticles Slows Spread of Brain Cancer
By combining nanoparticles with a scorpion venom compound already
being investigated for treating brain cancer, University of Washington
researchers found they could cut the spread of cancerous cells by 98
percent, compared to 45 percent for the scorpion venom alone.
"People talk about the treatment being more effective with
nanoparticles but they don't know how much, maybe 5 percent or 10
percent," said Miqin Zhang, professor of materials science and
engineering. "This was quite a surprise to us." She is lead author of a
study recently published in the journal Small.
For more than a decade scientists have looked at using
chlorotoxin, a small peptide isolated from scorpion venom, to target
and treat cancer cells.
Chlorotoxin binds to a surface protein overexpressed by many
types of tumors, including brain cancer. Previous research by Zhang's
group combined chlorotoxin with nanometer-scale particles of iron
oxide, which fluoresce at that size, for both magnetic resonance and
optical imaging.
Chlorotoxin also disrupts the spread of invasive tumors –
specifically, it slows cell invasion, the ability of the cancerous cell
to penetrate the protective matrix surrounding the cell and travel to a
different area of the body to start a new cancer. The MMP-2 on the
cell's surface, which is the binding site for chlorotoxin, is
hyperactive in highly invasive tumors such as brain cancer. Researchers
believe MMP-2 helps the cancerous cell break through the protective
matrix to invade new regions of the body. But when chlorotoxin binds to
MMP-2, both get drawn into the cancerous cell.
Other researchers are currently conducting human trials using chlorotoxin to slow cancer's spread.
Zhang's group investigated chlorotoxin action when it is
attached to nanoparticles and found the resultant complex doubles the
therapy's effect compared to chlorotoxin alone. Adding nanoparticles
often improves a therapy, partly because the combination lasts longer
in the body and so has a better chance of reaching the tumor. Combining
also boosts the effect because therapeutic molecules clump around each
nanoparticle. In the newly published study an average of 10 chlorotoxin
molecules were attached to each nanoparticle. Each clump thus offers
many therapeutic molecules that can simultaneously latch on to many
MMP-2 proteins.
Experiments were performed using mouse brain-cancer cells that
were grown in the lab. The imaging results confirm that adding
nanoparticles means more of the MMP-2 ends up safely tucked away inside
the cell, thus preventing MMP-2 from helping the cancer spread.
Further images showed that the cells containing nanoparticles
plus chlorotoxin were unable to elongate, whereas cells containing only
nanoparticles or only chlorotoxin could stretch out. This suggests that
the nanoparticle-plus-chlorotoxin disabled the machinery on the cell's
surface that allows cells to change shape, yet another step required
for a tumor cell to slip through the body.
"We hypothesized the mechanism and we have all the data to
prove our hypothesis," Zhang said. Further experiments will involve
testing on mice.
So far most cancer research has combined nanoparticles either
with chemotherapy that kills cancer cells, or therapy seeking to
disrupt the genetic activity of a cancerous cell. This is the first
time that nanoparticles have been combined with a therapy that
physically stops cancer's spread.
Slowing the spread of cancer would be especially useful for
treating highly invasive tumors such as brain cancer. MMP-2 also shows
signs of being overactive in cancers of the breast, colon, skin, lung,
prostate and ovaries, and researchers believe that the technique could
slow the spread of these other tumors.
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Co-authors are Omid Veiseh, Jonathan Gunn, Forrest Kievit,
Conroy Sun and Chen Fang of the UW and Jerry Lee of the National Cancer
Institute and Johns Hopkins University. The research was funded by the
National Institutes of Health and fellowships from the National Cancer
Institute and Ford Motor Company.
For more information, contact Zhang at 206-616-9356 or mzhang@u.washington.edu.
Public release date: 16-Apr-2009
Contact: Hannah Hickey
hickeyh@u.washington.edu
206-543-2580
University of Washington
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