“Trojan horse” anticancer system hides tumor-killing drug in fat cells
A new drug delivery system has been developed that hides chemotherapy molecules inside fat cells that are quickly eaten up by hungry tumors. The method has been shown to be effective at targeting bone, colon and pancreatic cancers in animals, and human trials are proposed for the near future.
Over the last few years scientists have discovered that although cancers generally prefer consuming sugars to grow, some also have quite an appetite for fat cells. Capitalizing on this mechanism, a team from Northwestern University has engineered a novel long-chain fatty acid molecule with binding sites on either end designed to hide cancer-killing drugs.
"It's like the fatty acid has a hand on both ends: one can grab onto the drug and one can grab onto proteins," says Nathan Gianneschi, lead on the new research. "The idea is to disguise drugs as fats so that they get into cells and the body is happy to transport them around."
Gianneschi explains that the engineered fatty acid molecule homes in on a cancer cell by hitchhiking on fat transport proteins, "both in the blood, and by engaging fat transport receptors on the surface of cancer cells."
"It's like a Trojan horse," he says. "It looks like a nice little fatty acid, so the tumor's receptors see it and invite it in. Then the drug starts getting metabolized and kills the tumor cells."
In early animal tests the researchers used the engineered fat molecule to transport paclitaxel, a common chemotherapy drug used to treat a variety of cancers. As well as effectively targeting and killing three different kinds of cancers, the animal studies revealed the dose of the drug could be significantly increased without becoming toxic.
The molecule could strikingly carry a dose of paclitaxel that was 20 times stronger than what is currently used. And even more impressively, this stronger dose was found to be 17 times safer than standard dosages.
"Commonly used small-molecule drugs get into tumors – and other cells," says Gianneschi. "They are toxic to tumors but also to humans. Hence, in general, these drugs have horrible side effects. Our goal is to increase the amount that gets into a tumor versus into other cells and tissues. That allows us to dose at much higher quantities without side effects, which kills the tumors faster."
It's still early days for the research but the team has founded an independent company called Vybyl Biopharma with plans to pursue further development and human clinical trials.
The new research was published in the Journal of the American Chemical Society.