New Targeted Therapy: Nanotechnology Breakthrough Allows Chemotherapeutic Agents To Cross Blood-Brain Barrier, Target Astrocytoma Cells
Two major challenges of treating glioblastoma multiforme have been the type and location of these aggressive brain tumors.¹ Surgical tumor resection is difficult due to the widespread nature of gliomas. Chemotherapeutic treatments are often unable to cross the blood-brain barrier or cannot be confined to cancerous cells only, thus causing toxicity in normal tissue.¹ One viable option is targeted therapy, which can result in both improved chemotherapeutic and surgical results.
Research initiated by Achuthamangalam Madhankumar, PhD, assistant professor of neurosurgery at Penn State Milton S. Hershey Medical Center, has shown it is possible to use targeted nanovesicles to carry anti-cancer drugs or contrast agents selectively to tumor cells. The latter approach enhances tumor visibility, enabling the surgeon to more accurately assess the extent of the tumor. In addition, because of the unique expression of the interleukin-13 (IL-13) receptor on certain types of brain tumors, this targeted delivery system may be useful in the diagnosis of tumors.
The research used a murine model to test parameters including the efficacy of targeted versus untargeted liposomal doxorubicin, a chemotherapeutic agent.¹ Mice with intracranial tumors measuring five millimeters received fifteen milligrams of doxorubicin for each kilogram of body weight once a week.¹ Over six weeks, the size of the tumor decreased to less than one millimeter in the group receiving targeted liposomes, but did not decrease in the two of eight surviving mice receiving untargeted liposomes with doxorubicin.¹ There was a significant decrease in the tumor volume on contrast MRI images in the targeted liposome group, as seen in the figure.¹
Based on this research, Penn State Hershey has been selected by the National Cancer Institute to form a collaboration to test this nanotechnology delivery system. Now that the initial characterization step with nanovesicles is complete, dramatic data are available showing the success of the system in destroying brain tumors in mice, and toxicology assays are underway. Penn State Hershey plans to begin Phase I human clinical trials later this year.
In the words of James R. Connor, PhD, distinguished professor of neurosurgery at Penn State Hershey, “With targeted therapy, we have a way of making both chemotherapeutic agents and radiation work more efficiently in cancer cells, providing better results with smaller doses.”
- Madhankumar AB, Slagle-Webb B, Wang X, Yang QX, Antonetti DA, Miller PA, Sheehan JM, and Connor JR. Efficacy of interleukin-13 receptor–targeted liposomal doxorubicin in the intracranial brain tumor model. Mol Cancer Ther 2009;8(3),648-654.