What's Next In Science & Technology

University of Michigan scientists have created the nanotechnology equivalent of a Trojan horse to smuggle a powerful chemotherapeutic drug inside tumor cells, thus increasing the drug's cancer-killing activity and reducing its toxic side effects.

"This is the first study to demonstrate a nanoparticle-targeted drug actually leaving the bloodstream, being concentrated in cancer cells, and having a biological effect on the animal's tumor."

"Targeting drugs directly to cancer cells reduces the amount that gets to normal cells, increases the drug's anti-cancer effect and reduces its toxicity. By improving the therapeutic index of cancer drugs, we hope to turn cancer into a chronic, manageable disease."

The drug delivery vehicle used by U-M scientists is a manmade polymer molecule called a dendrimer. Less than five nanometers in diameter, these dendrimers are small enough to slip through tiny openings in cell membranes. One nanometer equals one-billionth of a meter, which means it would take 100,000 nanometers lined up side-by-side to equal the diameter of a human hair.

Dendrimers have a tree-like structure with many branches where scientists can attach a variety of molecules, including drugs.

Folic acid, or folate, is an important vitamin required for the healthy functioning of all cells. But cancer cells, in particular, seem to need more than average amounts. To soak up as much folate as possible, some cancer cells display more docking sites called folate receptors on their cell membranes. By taking advantage of a cancer cell's appetite for folate, U-M scientists are able to prevent the cells from developing resistance to chemotherapeutic drugs.

"It's like a Trojan horse. Folate molecules on the nanoparticle bind to receptors on tumor cell membranes and the cell immediately internalizes it, because it thinks it's getting the vitamin it needs. But while it's bringing folate across the cell membrane, the cell also draws in the methotrexate that will poison it."

When tested in laboratory mice, the nanoparticle-based therapy was 10 times more effective at delaying tumor growth than a drug given alone. Nanoparticle treatment also proved to be far less toxic to mice in the study than the anticancer drug alone.

"Effectively, we achieved a 30-day tumor growth delay. Taking into account the length of a mouse's life, that is significant. One month for a mouse is about three years for a person."

By attaching different targeting molecules and different drugs to the nanoparticle, scientists eventually will be able to develop effective therapies for many types of cancer, perhaps even personalized therapy for an individual's specific cancer.