Researchers at Mayo Clinic have developed a new and promising method to deliver treatment directly to tumors of cholangiocarcinoma, a rare and aggressive cancer of the bile ducts with limited therapeutic options. They use milk-derived nanoparticles that act as targeted delivery vehicles. These nanoparticles, derived from milk, were loaded with small interfering RNA (siRNA) and functionalized with a tumor-targeting aptamer. This enabled the direct administration of gene therapy to cancer cells. "We demonstrated that this system could deliver gene-silencing therapy directly to the tumor," says Brandon Wilbanks, Ph.D., a postdoctoral researcher at Mayo Clinic and the study's first author. This led to a decrease in tumor growth and an increase in cancer cell death without damaging surrounding healthy tissues. Although the results are preclinical, the technology has been patented by Mayo Clinic, and researchers are now working to optimize genetic targets and evaluate the approach in multiple forms of cholangiocarcinoma. The research team used a gene therapy strategy based on small interfering RNA (siRNA), a molecule capable of temporarily silencing specific genes. The team examined a vast library of 600 trillion random DNA molecules to identify those that could selectively bind to the surface of cancer cells. Using a technique called Cell-SELEX, they discovered a short chain of DNA, known as an aptamer, that acts as a molecular navigation device, allowing it to locate and bind to cholangiocarcinoma cells. This navigation device was coupled to tiny lipid particles derived from milk, previously developed by Tushar Patel, M.B., Ch.B., a transplant hepatologist and also a researcher at Mayo Clinic in Florida, as a biocompatible way to transport treatments through the body. "They show that it might be possible to develop safer and more personalized treatments for patients who currently have very limited options," the study states. The long-term goal is to develop patient-specific gene therapies administered through this milk-derived platform to improve clinical outcomes.
