Chemotherapy drug resistance contributes to treatment failure
in more than 90% of metastatic cancers. Overcoming this hurdle would improve
cancer survival rates.
Dean Ho, an associate professor of biomedical engineering
and mechanical engineering at Northwestern
Univ., believes a tiny
carbon particle called a nanodiamond may offer an effective drug delivery
solution for hard-to-treat cancers.
In studies of liver and breast cancer models in vivo, Ho and a multidisciplinary team
of scientists, engineers, and clinicians found that a normally lethal amount of
a chemotherapy drug when bound to nanodiamonds reduced the size of tumors in
mice. Survival rates also increased and no toxic effects on tissues and organs
This is the first work to demonstrate the significance and
translational potential of nanodiamonds in the treatment of
chemotherapy-resistant cancers. The results are published in Science
“Our results show the nanodiamond’s enormous translational
potential towards significantly improving the efficacy of drug-resistant cancer
treatment and simultaneously improving safety,” said Ho, who led the research
and is corresponding author of the paper. “These are critical benefits. We
chose to study these chemo-resistant cancers because they remain one of the
biggest barriers to treating cancer and improving patient survival.”
Nanodiamonds are carbon-based materials approximately 2 to 8
nm in dia. Each nanodiamond’s surface possesses functional groups that allow a
wide spectrum of compounds to be attached to it, including chemotherapy agents.
The researchers took these nanodiamonds and reversibly bound
the common chemotherapy drug doxorubicin to them using a scalable synthesis
process, which enhances sustained drug release.
Ho and his colleagues studied mouse models with liver and
breast cancers. In these resistant cancers, drugs are able to get inside the
tumors but are kicked right back out because of an innate response in the liver
and breast to expel these drugs.
They treated one group of animals with the doxorubicin-nanodiamond
complexes and another group with the drug alone. In those treated with the
nanodiamond complexes, the chemotherapeutic remained in circulation longer—up
to 10 times longer—than those treated with the drug alone. In addition, the
drug itself was retained within both types of tumors for a significantly longer
period of time. Such a high retention rate means a smaller amount of the very
toxic drug would need to be administered, thus reducing side effects.
The researchers also found that the drug-nanodiamond
complexes had no negative effect on the white blood cell count. This is
important for cancer treatment: if the white blood cell count drops below a
certain level, treatment is stopped due to the risk of major complications.