Nanodiamond System Used to Deliver Chemotherapy Directly to Brain Tumors

The study was a collaboration between Dr. Dean Ho, professor, division of oral biology and medicine, division of advanced prosthodontics, and department of bioengineering and co-director of the Weintraub Center for Reconstructive Biotechnology at the University of California, Los Angeles’ (UCLA; USA) School of Dentistry and colleagues from the Lurie Children’s Hospital (Chicago, IL, USA) and Northwestern University Feinberg School of Medicine (Chicago, IL, USA).

Glioblastoma is the most common and lethal type of brain tumor. In spite of surgical treatment, radiation, and chemotherapy, median survival time of patients with glioblastoma is less than 1.5 years. This tumor is notoriously difficult to treat in part because chemotherapy drugs injected on their own often are unable to cross the blood-brain barrier, which is the system of protective blood vessels that surround the brain. Also, most drugs do not stay concentrated in the tumor tissue long enough to be effective.

The drug doxorubicin (DOX) is a common chemotherapy agent that is a promising treatment for a broad range of cancers, and served as a model drug for treatment of brain tumors when injected directly into the tumor. Dr. Ho’s team originally developed a strategy for strongly attaching DOX molecules to ND surfaces, creating a combined substance called ND-DOX.

Nanodiamonds can carry a wide range of drugs and prevent the ejection of drug molecules that are injected on their own by proteins found in cancer cells. Therefore, the ND-DOX remains in the tumor longer than DOX alone, exposing the tumor cells to the agent much longer without affecting the tissue surrounding the tumor.

Dr. Ho and colleagues hypothesized that glioblastoma might be effectively treated with a nanodiamond-modified drug using a technique called convection-enhanced delivery (CED), by which they injected ND-DOX directly into brain tumors in rodent models. The researchers found that the ND-DOX levels in the tumor were retained for a time period much longer than that of DOX alone. The DOX was taken into the tumor and remained in the tumor longer when attached to NDs. ND-DOX also increased programmed cell death and decreased cell viability in glioma (brain cancer) cell lines.

The study’s findings also revealed for the first time that ND- DOX delivery limited the amount of DOX that was distributed outside the tumor and reduced toxic side effects while keeping the drug in the tumor longer and increasing tumor-killing effectiveness for brain cancer treatment. The therapy was more effective and survival time increased substantially in rats treated with ND-DOX compared to those given unmodified DOX. Additional studies will increase the number of brain cancer-chemotherapy drugs that can be attached to the ND surface to optimize treatment and reduce side effects.

“Nanomaterials are promising vehicles for treating different types of cancer,” Dr. 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.”

Dr. Ho also noted that the ND has many aspects, almost similar to surface of a soccer ball, and can bind to DOX very strongly and quickly. To have a nanoparticle that has translational significance it has to have as many advantages as possible modified into one system as simply as possible. CED of ND-DOX offers a powerful treatment delivery system against these extremely difficult and lethal brain tumors.

The study appears in the advance online August 2013 issue of the journal Nanomedicine: Nanotechnology, Biology and Medicine.

Related Links:
University of California, Los Angeles
Northwestern University Feinberg School of Medicine