‘Trojan horse’ disguises chemo as fat

A stealthy new drug-delivery system disguises chemotherapy drugs as fat in order to outsmart, penetrate, and destroy tumors. Thinking the drugs are tasty fats, tumors invite the drug inside. Once there, the targeted drug activates, immediately suppressing tumor growth. The…

A stealthy new drug-delivery system disguises chemotherapy drugs as fat in order to outsmart, penetrate, and destroy tumors.

Thinking the drugs are tasty fats, tumors invite the drug inside. Once there, the targeted drug activates, immediately suppressing tumor growth. The drug also is lower in toxicity than current chemotherapy drugs, leading to fewer side effects. “It’s like a Trojan horse,” Nathan Gianneschi, a professor chemistry and of biomedical engineering and materials science and engineering in the McCormick School of Engineering and associate director of the International Institute of Nanotechnology at Northwestern University. “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.” Chemotherapy undercover To develop the targeting system, Gianneschi and his team engineered a long-chain fatty acid with two binding sites—able to attach to drugs—on each end. The fatty acid and its hitchhiking drugs are then hidden inside human serum albumin (HSA), which carries molecules, including fats, throughout the body. The body’s cellular receptors recognize the fats and proteins supplied by the HSA and allow them inside. Quick-growing and hungry, cancer cells consume the nutrients much faster than normal cells. When the cancer cells metabolize the hidden drug, they die. “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.” More drug, fewer side effects In the study, the researchers used the drug delivery system to carry a common, FDA-approved chemotherapy drug, paclitaxel, into tumors in a small animal model. Disguised as fat, the drug entered and completely eliminated the tumors in three types of cancer: bone, pancreatic, and colon. Even better: the researchers found they could deliver 20 times the dose of paclitaxel with their system, compared to two other paclitaxel-based drugs. But even at such a high quantity, the drug in Gianneschi’s system was still 17 times safer. “Commonly used small-molecule drugs get into tumors—and other cells,” Gianneschi says. “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 appears in the Journal of the American Chemical Society. Support for the study came from Elevance Renewable Sciences, the ARCS Foundation, and the Inamori Foundation. Source: Amanda Morris for Northwestern University