Mayo Clinic advances two nanoparticle cancer therapies in separate research programs

Mayo Clinic researchers are advancing two separate nanoparticle-based approaches to cancer treatment, one targeting aggressive bile duct cancer with milk-derived delivery vehicles and another using magnetic nanoparticles to heat tumors in metastatic disease.

In the first program, researchers have developed a method to deliver treatment directly to cholangiocarcinoma tumors 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. The multidisciplinary research team 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 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.

This system could deliver gene-silencing therapy straight to the cancer, leading 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. 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.

In a separate program, Mayo Clinic collaborated with New Phase Ltd. to install the first magnetic nanoparticle-mediated hyperthermia machine for cancer research in the U.S. Hyperthermia is a procedure that uses heat to damage and kill cancer cells. The investigational machine will support research evaluating the safety, feasibility and potential effectiveness of this approach in cancer treatment.

The investigational hyperthermia machine is an electromagnetic induction system that targets the torso. Doctors first administer iron oxide-containing magnetic nanoparticles through an IV, allowing them to collect in tumors. The care team then positions the patient in the machine, where electromagnetic waves heat the tumors to help destroy cancer cells. Induction cooktops require special pans to interact with the device. Instead of pans, the tumor absorbs the nanoparticles, effectively turning it into an induction pan. When alternating magnetic fields pulse the pan, it creates heat. A special coating on the nanoparticles limits the temperature to no more than 50 degrees Celsius. The care team also places cooling blankets on patients to keep their body temperature from rising too high and monitors them closely. The hope is that this controlled heating can damage the tumor to slow or stop its growth.

New Phase Ltd. manufactures both the hyperthermia machine and the nanoparticles. Mayo Clinic installed the machine within the Radiation Oncology Department in the Jacobson Building at Mayo Clinic in Rochester. The team completed the installation in November 2025. The first U.S. patient then received hyperthermia as part of a clinical trial in December 2025.

In the clinical trial, researchers are administering the investigational therapy to metastatic solid tumors in any body area except the brain. The investigational therapy can be administered to multiple tumors simultaneously and to cancers that are deep in the body. Researchers are focusing on patients whose cancers are resistant to multiple lines of systemic therapies and other advanced treatments, including radiotherapy. Researchers also plan to study hyperthermia in combination with other treatments, such as radiation. Combination therapy could allow for lower radiation doses with the same effectiveness or improve outcomes in radiation-resistant tumors.

Twenty years ago, Mayo Clinic radiation oncologists used ultrasound to heat water-filled bags that were placed on patients' skin, often on the chest wall of women who had recurrent breast cancer after surgery and radiation. However, the water bag temperature was unreliable, and patients could experience pain, causing the technique to fall out of favor. Other studies showing the benefits of hyperthermia combined with radiation were also limited by technological constraints.

Mayo Clinic has a financial interest in the technology referenced in the hyperthermia program. Mayo Clinic will use any revenue it receives to support its not-for-profit mission in patient care, education and research.