The Future is Small: Nanotechnology promises big changes for head and neck surgery

In the current in vivo investigation, mice with tumor xenographs expressing a range of folic acid receptors, from high expression (cancerous) to mid-range to none (healthy tissue), were exposed to dendrimer particles spiked with multiple conjugates of the anti-folate drug methotrexate.

Because of the dendrimer’s ability to access the target, flowing through the smallest leak in the tumor’s leaky vasculature and bringing multiple chemotherapeutic molecules to bear, the construct was able to extend the survival of over-expressing mice. The reason? More drug reached and remained on target. “These are much higher doses than [are] being delivered in the free methotrexate realm,” said Dr. Ward, “and the more dose you can give the animal, the greater the effects are going to be—sort of a no-brainer. But despite the fact that we are giving much larger doses, the systemic toxicity that we are seeing is much less.”

According to Dr. Ward, once the methotrexate is attached to the device, it can’t get back out of the cell. “It tends to stay around the tumor longer and not be exported by the normal cellular mechanisms,” he said. If his theory is correct, dendrimer conjugates may be able to block the development of chemotherapy resistance.

With this proof of principle in hand, Dr. Ward and colleagues are looking toward the development of an EGFR construct (think, cetuximab) specifically intended to treat head and neck cancer. Hopefully, it will provide proof once again that good things do come in small packages. ENT TODAY