Turn-on probes pinpoint cancer cells

By Shoshana Solomon

Illustration of image-guided surgery using the probes that light up in the presence of cancerous cells, technology that was developed by researchers at the Tel Aviv University. (IIlustrated by Maayan Harel)

Illustration of image-guided surgery using the probes that light up in the presence of cancerous cells, technology that was developed by researchers at the Tel Aviv University. 

Researchers at Tel Aviv University have developed smart nanoprobes that turn on a florescent light in presence of cancerous cells, which they say “may dramatically improve” post-surgical outcomes for cancer patients.

The researchers created a so called “smart probe” that, when injected into a patient a few hours before surgery to excise a primary tumor, may help surgeons pinpoint where the cancer is situated down to several cancer cells, permitting them to guarantee the removal of more cancer cells, and with the least possible damage to surrounding healthy tissue, they said in a statement.

The interdisciplinary team behind the research was led by Prof. Ronit Satchi-Fainaro, chair of the Department of Physiology and Pharmacology at TAU’s Sackler Faculty of Medicine. The study was published in May in Theranostics.

“In cases of melanoma and breast cancer, for example, the surgeon may believe he has gotten everything — that he has excised the entire tumor and left the remaining tissue free of cancer. Even if only a few cells linger after surgery, too few or too small to be detected by MRI or CT, recurrence and metastasis may occur,” Satchi-Fainaro says. “Our new technology can guide the surgeon to completely excise the cancer.”

The researchers based their work on previous studies, which showed that cancerous cells have an increased number of enzymes called cysteine cathepsins, which are present in high numbers in a variety of tumors. Healthy cells have small quantities of these cathepsins. Based on that knowledge, the researchers designed the probes to identify the cancer cells,” Satchi-Fainaro said in a statement.

Prof. Ronit Satchi-Fainaro, chair of the Department of Physiology and Pharmacology at TAU’s Sackler Faculty of Medicine

“We exploited this property,” of the increased number of cathepsins, “in order to design several Turn-ON probes, which can be activated to generate a fluorescence signal upon reaction with tumor cathepsins,” the researchers said in their study.

In the surrounding healthy tissue, because of a lack of cathepsins, the area remains dark.

The smart probes may be able to be used to guide the surgeon in real time during tumor excision. The surgeon can also avoid cutting out any “non-glowing” healthy tissue, the statement said.

The scientists first examined the effect of the probe in the lab on regular healthy skin and mammary tissue, and then on melanoma and breast cancer cells. They subsequently used mouse models of melanoma and breast cancer to perform routine tumor excision surgeries and smart probe-guided surgeries.

“The mice that underwent regular surgery experienced recurrence and metastasis much sooner and more often than those who underwent our smart probe-guided surgery,” Satchi-Fainaro said. “Most importantly, those that experienced the smart probe surgery survived much longer.”

Mice operated on without the probes were soon diagnosed with metastasis or recurrence of the tumors themselves, and their life expectancy was short — only 40 percent of the mice in this group survived 120 days postoperatively, the university said, in its statement in Hebrew. When the surgery was performed with the probes, however, the mice survival rate doubled: 80% remained healthy after 120 days. In other words, 60% of the mice operated in the ordinary manner died from the disease, compared to only 20% of those who underwent an operation using the smart probes, the statement said.

“The probe may also reduce the need for repeated surgeries in patients with cancer cells that remain in the edges of removed tissue,” Satchi-Fainaro said.  “Altogether, this may lead to the improvement of patient survival rates.”

The team has registered a number of patents on the development, and is also in talks with a number of pharmaceutical companies to start clinical trials toward commercialization of the technology, the statement said.

The Satchi-Fainaro laboratory’s research leading to these results received partial funding from the European Research Council (ERC) under the European Union’s Seventh Framework Programme.

The scientists who conducted the research for the study with Satchi-Fainaro included Rachel Blau, Yana Epshtein and Evgeni Pisarevsky, and the research was in collaboration with Prof. Doron Shabat of TAU’s School of Chemistry, Prof. Galia Blum of the Hebrew University in Jerusalem, and clinicians Prof. Zvi Ram and Dr. Rachel Grossman of the Department of Neurosurgery at Tel Aviv Medical Center.