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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.
About The National Cancer Institute (NCI)
To help meet the goal of reducing the burden of cancer, the National Cancer Institute (NCI), part of the National Institutes of Health, is engaged in efforts to harness the power of nanotechnology to radically change the way we diagnose, treat and prevent cancer.
The NCI Alliance for Nanotechnology in Cancer is a comprehensive, systematized initiative encompassing the public and private sectors, designed to accelerate the application of the best capabilities of nanotechnology to cancer.
Currently, scientists are limited in their ability to turn promising molecular discoveries into benefits for cancer patients. Nanotechnology can provide the technical power and tools that will enable those developing new diagnostics, therapeutics, and preventives to keep pace with today’s explosion in knowledge.
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