Nanoparticles transport cancer-killing drug into tumor cells to increase efficacy, lower drug toxicity in mice
- University of Michigan scientists have created the nanotechnology equivalent of a Trojan horse to smuggle a powerful chemotherapeutic drug inside tumor cells – increasing the drug's cancer-killing activity and reducing its toxic side effects.
They hooked folate and methotrexate to a manmade polymer molecule called a dendrimer, a tree like nanomolecule. The cancer cells have a high affinity for the folate and concentrate it. The methotrexate just came along for the ride.
- “It's like a Trojan horse,” Baker explains. “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 that had received injections of human epithelial cancer cells, the nanoparticle-based therapy using folic acid and methotrexate was 10 times more effective at delaying tumor growth than the drug given alone. Nanoparticle treatment also proved to be far less toxic to mice in the study than the anticancer drug alone.
“In our longest trial, which lasted 99 days, 30 percent to 40 percent of the mice given the nanoparticle with methotrexate survived,” says Jolanta Kukowska-Latallo, Ph.D., a U-M research investigator and first author of the study. “All the mice receiving free methotrexate died – either from overgrowth of the tumor or from toxic effects of the drug.