An anticancer "Trojan horse" disguises itself as fat

EVANSTON, Ill. – A new concealed drug delivery system conceals chemotherapy drugs in the form of fat to thwart, penetrate and destroy tumors.

Thinking that drugs are good fats, tumors invite drugs inside. Once on site, the targeted drug becomes active, immediately suppressing tumor growth. The drug is also less toxic than current chemotherapy drugs, resulting in fewer side effects.

"It's like a Trojan horse," Nathan Gianneschi, of Northwestern University, led the research. "It looks like a nice little fatty acid, so the tumor receptors see it and invite it in. Then the drug starts to be metabolized and kills the tumor cells."

The study will be published on 18 July in the Journal of the American Chemical Society (JACS). Gianneschi is Professor of Chemistry Jacob and Rosalind Cohn at the Weinberg College of Arts and Sciences in the North West Region. Cbadandra E. Callmann is the first author of the newspaper. Currently a postdoctoral fellow at Northwestern, Callmann was a graduate student from Gianneschi's laboratory during the research.

To develop the targeting system, Gianneschi and his team have developed a long-chain fatty acid with two binding sites that can bind to drugs at either end. The fatty acid and its hitchhiking medicines are then concealed in human serum albumin (HSA), which carries molecules, including fats, throughout the body.

Cellular receptors in the body recognize the fats and proteins provided by HSA and allow them inside. Fast growing and hungry, cancer cells consume nutrients much faster than normal cells. When the cancer cells metabolize the hidden drug, they die.

"It's as if the fatty acid had a hand at both ends: you could hang on to the drug and proteins," Gianneschi said. "The idea is to disguise the drugs into fats so that they enter the cells and that the body is happy to transport them."

In this study, researchers used the drug delivery system to introduce paclitaxel, a chemotherapy drug commonly approved by the FDA, into tumors of a small animal model. Disguised as fat, the drug entered and completely eliminated the tumors in three types of cancers: bone, pancreatic and colon cancers.

Better still: the researchers found that they could administer 20 times the dose of paclitaxel with their system, compared to two other paclitaxel-based medicines. But even with such a high amount, the drug in the Gianneschi system was still 17 times safer.

"The commonly used small molecule drugs are getting into tumors – and into other cells," Gianneschi said. "They are toxic to tumors, but also to humans, so these medications generally have terrible side effects.Our goal is to increase the amount that enters a tumor relative to others." This allows us to dose at much higher doses – no side effects, which kills tumors faster. "

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Associate Director of the Northwestern International Institute of Nanotechnology, Gianneschi is a member of the Institute of Life Process Chemistry, the Simpson Querrey Institute and the Robert H Cancer Research Center. Lurie. He is also Professor of Biomedical Engineering and Materials Science and Engineering at the McCormick School of Engineering.

The study was funded by Elevance Renewable Sciences, the ARCS Foundation and the Inamori Foundation.