Fluorescence Probe Paired with Engineered Enzymes Lights Up Tumors for Easier Surgical Removal

Successful cancer surgery relies on a surgeon’s ability to remove tumors while preserving as much healthy tissue as possible. To assist with this, surgeons often use fluorescent dyes that cause cancer cells to glow under special imaging systems. However, current dyes are not perfectly selective and can sometimes illuminate healthy tissue, making it difficult to distinguish tumors clearly during surgery. Researchers have now developed a new fluorescence system designed to highlight tumors with far greater precision.

Researchers at the University of Tokyo (Tokyo, Japan) have created what they describe as a bioorthogonal fluorescence probe paired with a specially engineered reporter enzyme that activates the probe only at targeted tumor sites. Unlike traditional probes that may be triggered by natural enzymes found throughout the body, this new probe remains inactive unless it encounters its matching engineered enzyme. This design significantly reduces unwanted background fluorescence.

To test the system, researchers delivered the engineered enzyme to tumor sites in mice with peritoneal cancer. Once the enzyme accumulated in the tumor tissue, the fluorescent probe was administered. The probe activated only when it encountered the engineered enzyme, causing the tumors to light up clearly. The study, published in American Chemical Society, shows that the approach allowed scientists to detect millimeter-sized tumor lesions with very low background fluorescence. The high contrast made tumors easier to distinguish from surrounding healthy tissue, potentially improving surgical precision.

Researchers believe this technology could eventually help surgeons identify and remove tumors more accurately during cancer surgery. The enzyme–probe system may also be adaptable to other cancer types by modifying the tumor-targeting component, such as using antibodies that recognize specific tumor markers. In addition to imaging, the approach could potentially be used for targeted drug delivery, where therapeutic agents are activated only at tumor sites. However, the current results are based on mouse studies, and further research is required before the technology can be tested in humans.

“Older probes often light up healthy tissue by mistake, creating background noise, but our highly selective, or bioorthogonal, dye probe is designed to stay completely off unless it meets its matching engineered enzyme,” said Associate Professor Ryosuke Kojima. “In the near term, this system could become a powerful research tool, and in the longer term, it may help surgeons remove tumors more completely by clearly highlighting cancer cells.’

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