Two Breakthroughs in Cancer Detection and Visualization

Two separate research teams have published findings on new techniques designed to improve the detection and visualisation of cancer cells—one focusing on enhanced cell capture and signal amplification, and the other on intraoperative tumour imaging.

Metal-Coated Extracellular Vesicles for Enhanced Cancer Detection

Researchers at the University of Tokyo, led by Professor Keisuke Goda, have developed a method to engineer extracellular vesicles (EVs) coated with lanthanide metal ions, including europium and terbium.

Mechanism

The technique, termed "super homotypic targeting," utilizes sialic acid—a sugar found in abundance on cancer cell surfaces. The lanthanide ions bind strongly to sialic acid, increasing the binding strength between EVs and target cells.

Performance

According to the researchers, this approach increases binding strength by over 25 times. The team also developed a signal amplification process, reported to be approximately 10,000-fold, which they state enables the detection of a single cancer cell among billions of healthy cells.

"By decorating extracellular vesicle surfaces with these ions, we effectively added many extra 'grips,' so extracellular vesicles and cells of the same lineage bound to one another more strongly, and a capture process that used to take more than two days finished in about three hours."
— Tianben Ding, Assistant Professor at the University of Tokyo and co-author of the study

Ding added: "The biggest challenge was achieving both extreme sensitivity and extreme selectivity at the same time... We also developed a way to amplify the signal around 10,000 times, making even a single cancer cell detectable."

Applications

The platform is designed for two purposes: capturing cancer EVs for detection and labeling cancer cells to amplify detection signals.

Testing

The technique was demonstrated in cell cultures, in mice, and on human triple-negative breast cancer samples.

Enzyme-Probe System for Tumour Visualisation During Surgery

A separate team at the University of Tokyo, led by Associate Professor Ryosuke Kojima and Professor Yasuteru Urano, has developed a system designed to improve the visualisation of cancer cells during surgery.

Mechanism

The system consists of a specialized reporter enzyme delivered to tumors and a fluorescent probe that activates only in the presence of that specific enzyme. The probe is made resistant to activation by natural enzymes in the body. The reporter enzyme was developed through a process of directed evolution to ensure sufficient activation within a living organism.

Performance

In tests on mice with peritoneal cancer, the enzyme reached abdominal wall tumors, and the subsequent application of the probe resulted in illumination. The researchers reported that this enabled visualisation of millimeter-sized tumour lesions with minimal background noise.

"Older probes often activated healthy tissue, whereas the newly developed dye probe is designed to remain inactive unless it encounters its matching enzyme."
— Professor Ryosuke Kojima, Associate Professor at the University of Tokyo

Limitations and Future Applications

A significant challenge for clinical application noted by the researchers is ensuring the engineered enzyme does not provoke an immune response in patients. Kojima stated that in the short term, the system could serve as a research tool, and in the long term, it may assist surgeons in identifying cancer cells during procedures.

The system is described as potentially adaptable to various cancer types by modifying the tumor-targeting component. Additionally, the research may inform methods for highly targeted drug delivery. The team noted that trials are currently limited to mice, and further research is necessary before human trials can be considered.