ScienceDaily (Apr. 5, 2012) —
Nanotechnology offers powerful new possibilities for targeted cancer
therapies, but the design challenges are many. Northwestern University
scientists now are the first to develop a simple but specialized
nanoparticle that can deliver a drug directly to a cancer cell's nucleus
-- an important feature for effective treatment.
They also are the first to directly image at nanoscale dimensions how nanoparticles interact with a cancer cell's nucleus.
"Our drug-loaded gold nanostars are tiny hitchhikers," said Teri W.
Odom, who led the study of human cervical and ovarian cancer cells.
"They are attracted to a protein on the cancer cell's surface that
conveniently shuttles the nanostars to the cell's nucleus. Then, on the
nucleus' doorstep, the nanostars release the drug, which continues into
the nucleus to do its work."
Odom is the Board of Lady Managers of the Columbian Exposition
Professor of Chemistry in the Weinberg College of Arts and Sciences and a
professor of materials science and engineering in the McCormick School
of Engineering and Applied Science.
Using electron microscopy, Odom and her team found their drug-loaded
nanoparticles dramatically change the shape of the cancer cell nucleus.
What begins as a nice, smooth ellipsoid becomes an uneven shape with
deep folds. They also discovered that this change in shape after drug
release was connected to cells dying and the cell population becoming
less viable -- both positive outcomes when dealing with cancer cells.
The results are published in the journal ACS Nano.
Since this initial research, the researchers have gone on to study
effects of the drug-loaded gold nanostars on 12 other human cancer cell
lines. The effect was much the same. "All cancer cells seem to respond
similarly," Odom said. "This suggests that the shuttling capabilities of
the nucleolin protein for functionalized nanoparticles could be a
general strategy for nuclear-targeted drug delivery."
The nanoparticle is simple and cleverly designed. It is made of gold
and shaped much like a star, with five to 10 points. (A nanostar is
approximately 25 nanometers wide.) The large surface area allows the
researchers to load a high concentration of drug molecules onto the
nanostar. Less drug would be needed than current therapeutic approaches
using free molecules because the drug is stabilized on the surface of
The drug used in the study is a single-stranded DNA aptamer called
AS1411. Approximately 1,000 of these strands are attached to each
The DNA aptamer serves two functions: it is attracted to and binds to
nucleolin, a protein overexpressed in cancer cells and found on the
cell surface (as well as within the cell). And when released from the
nanostar, the DNA aptamer also acts as the drug itself.
Bound to the nucleolin, the drug-loaded gold nanostars take advantage
of the protein's role as a shuttle within the cell and hitchhike their
way to the cell nucleus. The researchers then direct ultrafast pulses of
light -- similar to that used in LASIK surgery -- at the cells. The
pulsed light cleaves the bond attachments between the gold surface and
the thiolated DNA aptamers, which then can enter the nucleus.
In addition to allowing a large amount of drug to be loaded, the
nanostar's shape also helps concentrate the light at the points,
facilitating drug release in those areas. Drug release from
nanoparticles is a difficult problem, Odom said, but with the gold
nanostars the release occurs easily.
That the gold nanostar can deliver the drug without needing to pass
through the nuclear membrane means the nanoparticle is not required to
be a certain size, offering design flexibility. Also, the nanostars are
made using a biocompatible synthesis, which is unusual for
Odom envisions the drug-delivery method, once optimized, could be
particularly useful in cases where tumors are fairly close to the skin's
surface, such as skin and some breast cancers. (The light source would
be external to the body.) Surgeons removing cancerous tumors also might
find the gold nanostars useful for eradicating any stray cancer cells in
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- Duncan Hieu M. Dam, Jung Heon Lee, Patrick N. Sisco, Dick T. Co, Ming Zhang, Michael R. Wasielewski, Teri W. Odom. Direct Observation of Nanoparticle–Cancer Cell Nucleus Interactions. ACS Nano, 2012; : 120322074956003 DOI: 10.1021/nn300296p