Strategic Medicine: Researchers Develop ‘Trojan Horse’ Drug That Tricks, Then Kills Cancer Cells

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EVANSTON, Ill. — The same tactics used by the ancient Greeks thousands of years ago in battle are being applied by researchers at Northwestern University to fight cancer today. A newly designed drug delivery system is capable of disguising chemotherapeutics as fat, a favorite snack of cancerous tumors, creating an effect likened to the “Trojan horse” tale heralded in Greek lore.

Ever since the ancient Greeks snuck their way into the city of Troy inside a giant wooden horse disguised as a gift, the tale of the Trojan horse has been considered a classic example of strategy and cunning over brute force. Now, researchers are hoping to use a bit of deception in the fight against cancer.

In order to develop this delivery and targeting system, researchers engineered a long-chain fatty acid capable of binding itself to drugs at both ends. The fatty acid, with drugs in tow, is then hidden inside a protein found in human blood that carries fat molecules throughout the body.

Essentially, tumors are “tricked” into inviting the chemotherapeutics inside, allowing the drug to destroy them from the inside out. After making it inside the tumor, the hidden drug activates and kills cancer cells. This innovative delivery method is also lower in toxicity, thus causing less harmful side effects than most other chemotherapy treatments available today.

“It’s like a Trojan horse,” lead researcher Nathan Gianneschi explains in a statement. “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.”

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In the study, researchers used the new delivery method to carry an FDA-approved chemotherapy drug called paclitaxel into tumors in a small animal model. The drugs entered and completely eliminated tumors carrying bone, pancreatic, and colon cancer.

“It’s like the fatty acid has a hand on both ends: one can grab onto the drug and one can grab onto proteins,” Gianneschi says. “The idea is to disguise drugs as fats so that they get into cells and the body is happy to transport them around.”

Additionally, this new delivery method was able to transport 20 times the dose of paclitaxel typically allowed by two older paclitaxel-based drugs. Amazingly, even with a significantly higher dose, the new Trojan horse method was still found to be 17 times safer than other paclitaxel-based drugs.

“Commonly used small-molecule drugs get into tumors — and other cells,” Gianneschi comments. “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.”

The study is published in the Journal of the American Chemical Society.

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