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Abstract:
Northwestern University researchers have shown that
nanodiamonds -- much like the carbon structure as that of a sparkling 14
karat diamond but on a much smaller scale -- are very effective at
delivering chemotherapy drugs to cells without the negative effects
associated with current drug delivery agents.

Nanoengineers mine tiny diamonds for drug delivery

EVANSTON, IL | Posted on October 12th, 2007

Their study, published online by the journal Nano Letters, is the first to
demonstrate the use of nanodiamonds, a new class of nanomaterials, in
biomedicine. In addition to delivering cancer drugs, the model could be used
for other applications, such as fighting tuberculosis or viral infections,
say the researchers.

Nanodiamonds promise to play a significant role in improving cancer
treatment by limiting uncontrolled exposure of toxic drugs to the body. The
research team reports that aggregated clusters of nanodiamonds were shown to
be ideal for carrying a chemotherapy drug and shielding it from normal cells
so as not to kill them, releasing the drug slowly only after it reached its
cellular target.

Another advantage of the material, confirmed by a series of genetic studies
also reported in the paper, is that nanodiamonds do not cause cell
inflammation once the drug has been released and only bare diamonds are
left. Materials currently used for drug delivery can cause inflammation, a
serious complication that can predispose a patient to cancer, block the
activity of cancer drugs and even promote tumor growth.

"There are a lot of materials that can deliver drugs well, but we need to
look at what happens after drug delivery," said Dean Ho, assistant professor
of biomedical engineering and mechanical engineering at Northwestern's
McCormick School of Engineering and Applied Science, who led the research.
"How do cells react to an artificial material left in the body? Nanodiamonds
are highly ordered structures, which cells like. If they didn't, cells would
become inflamed. From a patient's perspective, this is very important. And
that's why clinicians are interested in our work."

"Novel drug delivery systems, such as the one being developed by Dean and
his team, hold great promise in cancer therapeutics," said Steven Rosen,
M.D., director of the Robert H. Lurie Comprehensive Cancer Center of
Northwestern University and Genevieve E. Teuton Professor of Medicine at
Northwestern's Feinberg School of Medicine. "We anticipate they will allow
for more sophisticated means of targeting cancer cells while sparing healthy
cells from a drug's toxicity."

To make the material effective, Ho and his colleagues manipulated single
nanodiamonds, each only two nanometers in diameter, to form aggregated
clusters of nanodiamonds, ranging from 50 to 100 nanometers in diameter. The
drug, loaded onto the surface of the individual diamonds, is not active when
the nanodiamonds are aggregated; it only becomes active when the cluster
reaches its target, breaks apart and slowly releases the drug. (With a
diameter of two to eight nanometers, hundreds of thousands of diamonds could
fit onto the head of a pin.)

"The nanodiamond cluster provides a powerful release in a localized place --
an effective but less toxic delivery method," said co-author Eric
Pierstorff, a molecular biologist and post-doctoral fellow in Ho's research
group. Because of the large amount of available surface area, the clusters
can carry a large amount of drug, nearly five times the amount of drug
carried by conventional materials.

Liposomes and polymersomes, both spherical nanoparticles, currently are used
for drug delivery. While effective, they are essentially hollow spheres
loaded with an active drug ready to kill any cells, even healthy cells that
are encountered as they travel to their target. Liposomes and polymersomes
also are very large, about 100 times the size of nanodiamonds -- SUVs
compared to the nimble nanodiamond clusters that can circulate throughout
the body and penetrate cell membranes more easily.

Unlike many of the emerging nanoparticles, nanodiamonds are soluble in
water, making them clinically important. "Five years ago while working in
Japan, I first encountered nanodiamonds and saw it was a very soluble
material," said materials scientist Houjin Huang, lead author of the paper
and also a post-doctoral fellow in Ho's group. "I thought nanodiamonds might
be useful in electronics, but I didn't find any applications. Then I moved
to Northwestern to join Dean and his team because they are capable of
engineering a broad range of devices and materials that interface well with
biological tissue. Here I've focused on using nanodiamonds for biomedical
applications, where we've found success.

"Nanodiamonds are very special," said Huang. "They are extremely stable, and
you can do a lot of chemistry on the surface, to further functionalize them
for targeting purposes. In addition to functionality, they also offer safety
-- the first priority to consider for clinical purposes. It's very rare to
have a nanomaterial that offers both."

"It's about optimizing the advantages of a material," said Ho, a member of
the Lurie Cancer Center. "Our team was the first to forge this area --
applying nanodiamonds to drug delivery. We've talked to a lot of clinicians
and described nanodiamonds and what they can do. I ask, 'Is that useful to
you?' They reply, 'Yes, by all means.'"

For their study, Ho and his team used living murine macrophage cells, human
colorectal carcinoma cells and doxorubicin hydrochloride, a widely used
chemotherapy drug. The drug was successfully loaded onto the nanodiamond
clusters, which efficiently ferried the drug inside the cells. Once inside,
the clusters broke up and slowly released the drug.

In the genetic studies, the researchers exposed cells to the bare
nanodiamonds (no drug was present) and analyzed three genes associated with
inflammation and one gene for apoptosis, or cell death, to see how the cells
reacted to the foreign material. Looking into the circuitry of the cell,
they found no toxicity or inflammation long term and a lack of cell death.
In fact, the cells grew well in the presence of the nanodiamond material.

The work was supported by the National Institute of Allergy and Infectious
Diseases of the National Institutes of Health (grant U54 A1065359).

In addition to Ho, Huang and Pierstorff, the other author of the paper,
titled "Active Nanodiamond Hydrogels for Chemotherapeutic Delivery," is Eiji
Osawa, of the Nanocarbon Research Institute, Ltd., Chiba, Japan.

(Source contact: Dean Ho at office 847-467-0548, cell 310-570-0750 or
)