LDL-DHA Nanoparticles Selectively Eradicate Liver Tumors in Rat Model System

Uptake of low-density lipoprotein (LDL) particles loaded with the omega-3 fatty acid docosahexaenoic acid (DHA) by liver cancer cells resulted in destruction of established tumors in a rat liver cancer model.

While dietary intake of DHA has been implicated in protecting patients with viral hepatitis B or C from developing liver cancer, little is known about the effects of DHA on established solid tumors.

In order to deliver a higher concentration of DHA to liver cancer cells than could be achieved through the diet, investigators at the University of Texas Southwestern Medical Center (Dallas, USA) used modified LDL particles as a targeted delivery system.

The investigators administered normal LDL or LDL particles in which the cholesterol had been replaced by DHA to rats with established liver tumors. They found that control rats had large, highly vascularized tumors that contained proliferating cells. However, rats given LDL−DHA had smaller, pale tumors that were devoid of vascular supply and more than 80% of the tumor tissue was necrotic. Four to six days after injection of LDL−DHA, the tumors were three-fold smaller than those of control rats. The liver tissue that surrounded the tumors showed no histologic or biochemical evidence of injury.

Injection of LDL−DHA into the hepatic artery of rats selectively deregulated redox reactions in tumor tissues by increasing levels of reactive oxygen species and lipid peroxidation, depleting and oxidizing glutathione and nicotinamide adenine dinucleotide phosphate, and significantly down-regulating the antioxidant enzyme glutathione peroxidase-4. Remarkably, the redox balance in surrounding normal liver tissues was not disrupted.

“This approach offers a potentially new and safe way of treating liver cancer, and possibly other cancers,” said senior author Dr. Ian Corbin, assistant professor of medicine at the University of Texas Southwestern Medical Center. “The method utilizes the cholesterol carrier LDL, combined with fish oil to produce a unique nanoparticle that is selectively toxic to cancer cells.”

“This research study clearly demonstrates the anticancer potential of omega-3 fatty acids,” said Dr. Corbin. “We knew that cancer cells like to take up LDL in order to acquire cholesterol and other lipids to help build their cell membranes as they proliferate. So what we have here is a classic example of a Trojan horse. The cancer cell thinks it is getting cholesterol to provide the nutritional building blocks needed to grow and proliferate. Instead, it gets a payload of fish oil in the form of LDL-DHA nanoparticles that are selectively toxic to cancer cells without harming normal liver cells.”

The study was published in the February 2016 issue of the journal Gastroenterology.

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University of Texas Southwestern Medical Center