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New Nanoparticle Therapy Holds Potential for Safe Treatment of Liver Cancer

Researchers from UT Southwestern Medical Center have reported on an experimental nanoparticle therapy, which incorporates low-density lipoproteins (LDL) and fish oil to selectively destroy liver cancer cells without affecting the healthy cells.

This approach offers a potentially new and safe way of treating liver cancer, and possibly other cancers. The method utilizes the cholesterol carrier LDL, combined with fish oil to produce a unique nanoparticle that is selectively toxic to cancer cells.

Dr. Ian Corbin, Assistant Professor in the Advanced Imaging Research Center (AIRC) and of Internal Medicine at UT Southwestern.

This report appeared in the February issue of Gastroenterology.

In accordance with the National Cancer Institute (NCI), hepatocellular carcinoma, also known as primary liver cancer, as the sixth most widespread cancer form and the third most important cause of cancer-related deaths all over the world. The prevalence of the disease is increasing in the United States especially with regard to the increase of hepatitis C virus infection.

Dr. Ian Corbin (left) and Dr. Xiaodong Wen look over lab samples from their study of an experimental nanoparticle therapy that shows promise for fighting primary liver cancer.

An editorial in this February issue of Gastroenterology highlights that drug-based treatments for cancer involved with the liver are not available in plenty and a study by the UT Southwestern showed “truly remarkable results that should prompt further research under preclinical settings, given its potential to lead to a paradigm shift in treatment.” Some of the frequently used treatment methods include ablation, liver transplantation, and surgical resection.

Fish oils are known for its richness in omega-3 fatty acids like docosahexaenoic acids otherwise known as DHA. In 2012, Gastroenterology published a study, which discovered that consumption of fish oils with omega-3 fatty acids helps prevent the evolution of liver cancer in patients with hepatitis C or hepatitis B infections.

Dr. Corbin, stated that a number of studies have spoken about the relation that exist between cancer prevention and omega-3 fatty acids, and yet there are no studies highlighting the positive outcomes of using omega-3 fatty acids against tumors that have already been established. The present study points out that the established tumors will have to be exposed to increasing amounts of omega-3 fatty acids instead of being treated with a diet.

Dr. Corbin further pointed out that rats were used as part of the UT Southwestern study. The newly formulated LDL-DHA nanoparticles were injected into the artery leading to the rat’s liver, which is affected by cancer.

“This research study clearly demonstrates the anticancer potential of omega-3 fatty acids,” he said, adding that the study highlighted vital cancer cell toxicity but yet it is too soon to decide whether this new technique is capable of killing all cancer cells. Upcoming experiments will aim at analyzing this query and also study if the LDL-DHA strategy is capable of increasing the survival rate of cancer.
Dr. Corbin, a member of the Harold C. Simmons Comprehensive Cancer Center, headed a multidisciplinary team in order to develop and distinguish the unique nanoparticle formulation. This team was made up of researchers from different fields that include cancer biology, advanced imaging, lipid biochemistry, biotechnology, and nutritional science.

Dr. Corbin stated that this study is based on the UT Southwestern collaboration of Dr. Michael Brown and Dr. Joseph Goldstein in the late 1970s resulting in their 1985 Nobel Prize. These two individuals laid the foundation for the development of cholesterol-lowering statin drugs through their invention of the LDL receptor and their efforts to understand the functioning of the protein. Dr. Brown, Director of the Erik Jonsson Center for Molecular Genetics, holds the W.A. (Monty) Moncrief Distinguished Chair in Cholesterol and Arteriosclerosis Research. Dr. Goldstein, Chairman of Molecular Genetics, holds the Julie and Louis A. Beecherl, Jr. Distinguished Chair in Biomedical Research. Both are Regental Professors and hold the Paul J. Thomas Chair in Medicine.

In trying to understand the biology of the LDL receptor, they conducted reconstitution experiments in which they removed the usual cholesterol content from LDL and added different types of cholesterol molecules. In our study, we used that method to formulate LDL combined with DHA as a possible cancer treatment.

Dr. Ian Corbin, Assistant Professor in the Advanced Imaging Research Center (AIRC) and of Internal Medicine at UT Southwestern.

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’s 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.

Dr. Ian Corbin, Assistant Professor in the Advanced Imaging Research Center (AIRC) and of Internal Medicine at UT Southwestern.

The researchers used control treatments of LDL without DHA or the LDL-DHA nanoparticles on rats suffering from liver cancer, and they expected no effects. After a period of three days, the tumors in controls increased in size forming an efficient supply of blood, which play a vital role in the growth of cancer. In contrast, the LDL-DHA rats had pale and small tumors with poor supply of blood, and more than 80% of their tumor cells were actually dying.

In conclusion, our study demonstrates that LDL-DHA nanoparticles have potent anti-cancer activity.

UT Southwestern Research Team

UT Southwestern researchers contributing to this study included lead author Dr. Xiaodong Wen, senior research associate in the AIRC; Dr. Lacy Reynolds, former Cancer Biology graduate student; Dr. Rohit Mulik, former postdoctoral researcher in the AIRC; Soo Young Kim and Tim Van Treuren, former summer research fellows; Liem Nguyen, graduate student in Cancer Biology; and Dr. Hao Zhu, Assistant Professor in the Children’s Medical Center Research Institute at UT Southwestern, Internal Medicine, and Pediatrics.

This study was partially supported by the American Gastroenterological Association Research Foundation Scholar Award, the Southwestern Small Animal Imaging Research Program, the National Cancer Institute, and a UT Southwestern President’s Research Council Award.

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