Fluorescent Nanoprobe Produces ‘Breakthrough’ for Peritoneal Metastases

November 15, 2023

Nanotechnology produces ‘glow’ effect that enhances visibility of tumor edges, allowing surgeons to remove more cancer cells than standard imaging technology.

A pH-sensitive cancer therapy discovered at UT Southwestern Harold C. Simmons Comprehensive Cancer Center has been fast-tracked by the U.S. Food and Drug Administration for use as adjunct for visualization of metastases in the peritoneal cavity.

The real-time surgical imaging agent, called the fluorescent nanoprobe, uses nanotechnology to detect acidity and make the edges of solid metastatic tumors glow during cancer surgery. The enhanced visibility allows surgeons to remove cancer cells throughout the abdomen at 50%-60% higher rates than standard cancer imaging technology.

The fluorescent nanoprobe technology was developed by pharmacologist and distinguished researcher Jinming Gao, Ph.D., Professor at Simmons Cancer Center and of Pharmacology, Otolaryngology – Head and Neck Surgery, and Cell Biology, and Baran Sumer, M.D., Professor of Otolaryngology – Head and Neck Surgery. It is just the third imaging agent to receive the FDA’s Breakthrough Therapy Designation.

Early data from a phase two clinical trial shows the nanoprobe identifies 10 times more metastatic cancer cells than the FDA’s minimum 5% threshold for successful detection.

“In animal models, we saw that we could detect cancers down to a half-millimeter. We didn’t necessarily expect that level of specificity in human samples, but that’s what we got. It was a very, very nice surprise,” says Dr. Sumer.

The nanoprobe is delivered through an IV about 24 hours before surgery. As the imaging agent pegsitacianine circulates through the body, it “digitizes” the acidic signals from cancer cells. The nanoprobe is switched “off” while circulating in normal pH and turns “on” when the sensors detect acidity. When switched “on,” dissociated cationic polymers attach to the cancer cells, lighting them up under near-infrared light.

Using an intraoperative camera, the surgeon can better visualize the glowing cells and remove them with extreme precision. Pegsitacianine is designed to light up quickly in an acidic environment and also to be compatible with cameras integrated into surgical suites, including the da Vinci robot system.

Expanding Cancer Targets in the Future

Because the nanoprobe technology targets the Warburg effect, it is tumor-agnostic and could potentially be used in other forms of cancer.

Besides an award to study peritoneal metastasis, the National Cancer Institute has awarded
UT Southwestern a clinical R01 grant to study the use of the nanoprobe to locate unknown primary cancer in the head and neck. That trial is scheduled to open this year.

OncoNano Medicine Inc., a startup co-founded to commercialize the technology, has received a Small Business Innovation Research (SBIR) grant to further develop the technology and conduct a phase three clinical trial for metastatic peritoneal tumors. Once it earns FDA approval, the trial will be held at multiple U.S. centers, including UTSW.

Next up for the nanoprobe are two adaptations of the technology being tested in human studies:

A “nanovaccine” that trains the immune system to produce tumor-specific T cells to target the adaptor protein STING (stimulator of interferon genes) to initiate an immune response against the cancer.
Reversing the Warburg effect to neutralize the acidic tumor environment and keep the immune system functional to eliminate cancer cells.

At UT Southwestern, Dr. Gao and Dr. Sumer are continuing to push forward with research and creating more clinical applications for the nanoprobe.

Drs. Gao and Sumer each have financial interests in OncoNano Medicine Inc., as does UT Southwestern.

Baran Sumer, M.D., is Professor of Otolaryngology – Head and Neck Surgery and Chief of the Division of Head and Neck Oncology at UT Southwestern. He specializes in head and neck cancer surgery and reconstruction. Dr. Sumer is a member of the Experimental Therapeutics Research Program at Simmons Cancer Center.

Jinming Gao, Ph.D., is a Professor at Simmons Cancer Center and of Pharmacology, Otolaryngology – Head and Neck Surgery, and Cell Biology. His lab studies the science of nanotechnology and cancer. Dr. Gao is a member of the Experimental Therapeutics Research Program at Simmons Cancer Center.