Mayo Clinic researchers have developed a promising new way to deliver treatment directly to cholangiocarcinoma tumors, a rare and aggressive bile duct cancer with limited treatment options, using milk-derived nanoparticles that act like guided delivery vehicles. The findings, published in JHEP Reports, point to a potential targeted genetic therapy designed to attack cancer cells while sparing healthy tissue.
"One significant issue is the lack of medications that treat the specific alterations in these cancers," says Rory Smoot, M.D., surgical oncologist at Mayo Clinic in Rochester and senior author of the study. "Our approach is designed to turn off specific cancer-driving genes while leaving healthy tissue alone."
To do this, the multidisciplinary research team of researchers used a gene-therapy strategy involving small interfering RNA (siRNA), a molecule that can temporarily silence specific genes.
The team screened a vast library of 600 trillion random DNA molecules to find those that could selectively bind to the surface of cancer cells. Using a technique called Cell-SELEX, they discovered a short DNA strand, known as an aptamer, that works like a molecular homing device, enabling it to find and attach to cholangiocarcinoma cells.
That homing device was attached to tiny, fat-based particles made from milk, previously developed by Tushar Patel, M.B., Ch.B., a transplant hepatologist and researcher at Mayo Clinic in Florida, as a biocompatible way to carry treatments through the body. These milk-derived nanoparticles were loaded with siRNA and outfitted with the tumor-targeting aptamer, enabling direct delivery of genetic therapy into cancer cells.
"We showed that this system could deliver gene-silencing therapy straight to the cancer," says Brandon Wilbanks, Ph.D., postdoctoral research fellow at Mayo Clinic and first author of the study. "This led to decreases in cancer growth and an increase in cancer cell death, without harming nearby healthy tissues."
While the findings are preclinical, the technology has been patented by Mayo Clinic, and researchers are now working to optimize gene targets and test the approach across multiple forms of cholangiocarcinoma. The long-term goal is to develop patient-specific gene therapies delivered via this milk-derived platform to improve outcomes for patients.
"These advances bring real hope," says Dr. Smoot. "They show that it may be possible to develop safer, more personalized treatments for patients who currently have very limited options."
This research was funded by the Mayo Clinic RNA Discovery and Translation Program, the Mayo Clinic Department of Surgery, the Mayo Clinic Hepatobiliary SPORE NCI, the Mayo Clinic Center for Cell Signaling in Gastroenterology, JSPS KAKENHI Fostering Joint International Research, and the University of Wisconsin Biology of Aging and Age-Related Diseases.
The researchers report no conflicts of interest. Review the study for a complete list of authors, disclosures and funding.
