Nanodiamonds carry chemotherapy drugs direct to brain tumour
8 October 2013
Microscopic carbon-based particles
called nanodiamonds are able to carry chemotherapy drugs directly
into brain tumours in a new technique developed by the Jonsson Comprehensive Cancer Center
The new method was found to result in greater cancer-killing
efficiency and fewer harmful side effects than existing treatments.
The research has been published in the journal Nanomedicine: Nanotechnology, Biology and Medicine
Glioblastoma is the most common and
lethal type of brain tumour. Despite treatment with surgery,
radiation and chemotherapy, the median survival time for
glioblastoma patients is less than one-and-a-half years. The tumours
are notoriously difficult to treat, in part because chemotherapy
drugs injected alone often are unable to penetrate the system of
protective blood vessels that surround the brain, known as the
blood–brain barrier. And those drugs that do cross the barrier do
not stay concentrated in the tumour tissue long enough to be
The drug doxorubicin, a common chemotherapy
agent, has shown promise in a broad range of cancers, and it has
served as model drug for the treatment brain tumours when injected
directly into the tumour. Dean Ho of the UCLA School of Dentistry
and colleagues from the Lurie Children's Hospital of Chicago and
Northwestern University's Feinberg School of Medicine originally developed a strategy
for strongly attaching doxorubicin molecules to nanodiamond
surfaces, creating a combined substance called ND–DOX.
Nanodiamonds are carbon-based particles roughly 4 to 5 nanometers in
diameter that can carry a broad range of drug compounds. The
particles have a large accessible surface and tailorable surface
chemistry. They also have unique optical, mechanical, and thermal
properties and are non-toxic.
Tumour-cell proteins are able to eject most anticancer drugs that are
injected into the cell before those drugs have time to work, but they
can't get rid of the nanodiamonds. Thus, drug–nanodiamond
combinations remain in the cells much longer without affecting the
tissue surrounding the tumour.
ND-DOX in the brain. These images show the retention of
doxorubicin and ND-DOX in brain tissue, with light microscopic
images (upper rows) and fluorescence images detecting
fluorescence generated from doxorubicin (lower rows). The images
show the distribution of unmodified doxorubicin and ND-DOX after
convection-enhanced delivery (CED) at 6, 16, 24 and 72 hours.
Credit: Jonsson Comprehensive Cancer Center, UCLA
HHo and his colleagues
hypothesized that glioblastoma might be efficiently treated with a
nanodiamond-modified drug by using a direct-injection technique
known as convection-enhanced delivery, or CED. They used this method
to inject ND–DOX directly into brain tumors in rodent models.
The researchers found that ND–DOX levels in the tumours were retained
for a duration far beyond that of doxorubicin alone, showing that
doxorubicin was taken into the tumour and remained their longer when
attached to anodiamonds. In addition, ND–DOX was also found to
increase apoptosis — programmed cancer-cell death — and to decrease
cell viability in glioma (brain cancer) cell lines.
results also demonstrated for the first time that the ND–DOX
delivery limited the amount of doxorubicin that was distributed
outside the tumour. This reduced toxic side effects and kept more of
the drug in the tumour for longer, increasing the drug's
tumour-killing efficiency without affecting the surrounding tissue.
Survival time increased significantly in the rats treated with
ND–DOX, compared with those given only unmodified doxorubicin.
NNanodiamonds have many facets, almost like the surface of a soccer
ball, and can bind to doxorubicin very strongly and quickly, Ho
noted. Further research will expand the list of brain-cancer
chemotherapy drugs that can be attached to the nanodiamond surfaces
to improve treatment and reduce side effects.
"Nanomaterials are promising vehicles for treating different
types of cancer," Ho said. "We're looking for the drugs and
situations where nanotechnology actually helps chemotherapy function
better, making it easier on the patient and harder on the cancer."
This study showed that convection-enhanced delivery of ND–DOX offers
a powerful treatment delivery system against these very difficult
and deadly brain tumours, Ho said.