Biologically Targeted Nanoparticles May Boost
Radiation Therapy Effects
Making a tumor more sensitive to radiotherapy is a primary goal of combining chemo and radiation therapy to treat many types of cancer, but with the chemotherapy drugs come unwanted side effects. Now, investigators from the University of North Carolina report what they believe is the first pre-clinical demonstration of the potential of molecularly targeted nanoparticles as a promising new class of agents that can improve chemoradiotherapy treatment.
The nanoparticles target tumor cells, the investigators explain, thus sparing normal tissue and avoiding the systemic side effects often associated with chemotherapy drugs. The researchers, led by Andrew Wang, a member of the Carolina Center for Cancer Nanotechnology Excellence, reported their findings in the journal ACS Nano.
The team used docetaxel, a drug used to treat head and neck cancers. As Wang explained, "docetaxel is a proven drug used in chemoradiotherapy, but it leads to many unwanted side effects on normal organs. The nanoparticle formulation of docetaxel, on the other hand, concentrates in tumors, which in turn leads to improved efficacy and fewer side effects."
To accomplish this feat, the investigators developed a biodegradable polymeric lipid nanoparticle formulation of docetaxel that targets the folate receptor, overexpressed in head and neck and other tumors. Folate is a water-soluble form of Vitamin B9. "We found that the folate-targeted nanoparticle was more effective than the docetaxel or non-targeted nanoparticle formulations of docetaxel," said Wang. "We also learned that timing of the radiation following administration of the nanoparticle formulation is critical."
This last finding came about when the investigators first tested their nanoparticle formulation on tumor cells and observed that the targeted nanoparticle was less effective than free docetaxel as a radiosensitizer. Further investigation found that the timing of radiation after dosing was critical, with the two formulations displaying equal efficacy if radiation was postponed for 24 hours after dosing with the nanoparticle, compared to the one-hour delay used with free docetaxel. When tested in animals, Wang and his collaborators found that a 12-hour delay between the time of dosing and the time of irradiation produced the best results.
This information, he said, will be helpful in the clinical translation of nanoparticle drugs in chemoradiation. His group is currently evaluating two commercial formulations of nanoparticle taxane drugs in preparation for early phase clinical trials in the near future.
This work, which is detailed in a paper titled, "Folate-Targeted Polymeric Nanoparticle Formulation of Docetaxel Is an Effective Molecularly Targeted Radiosensitizer with Efficacy Dependent on the Timing of Radiotherapy," was supported in part by the NCI Alliance for Nanotechnology in Cancer, a comprehensive initiative designed to accelerate the application of nanotechnology to the prevention, diagnosis, and treatment of cancer. An abstract of this paper is available at the journal's website.