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The potentially breakthrough technology works for all types of cancers and is now in the works to be tested in humans early next year. (Credit: Dr. Esther de Boer)

A new nanotechnology technique can now resolve the challenge of malignant tumor detection due to strong genetic and histological differences in cancerous tissue.

The nanoscale fluorescent probes switch on in the presence of cancer cells, helping surgeons eliminate tumors in mice without harming healthy tissue, according to a study published early this week.

The potentially breakthrough technology works for all types of cancers and is now in the works to be tested in humans early next year.

The study was published in the peer-reviewed journal Nature Biomedical Engineering.

In the experiments, microscopic probes were injected into mice with cancerous tumors. A built-in ‘switch’ illuminates the probes when they come into contact with a cancer cell.

“The nanoprobe allowed us to image a broad range of tumors in mouse models using a variety of clinical cameras. We were able to perform real-time tumor-acidosis-guided detection and surgery of occult nodules in mice bearing head and neck or breast tumors, significantly lengthening mice survivability,” said the study.

For several cancers, surgery is the primary option for treatment. But making sure that no cancer cells are left during an operation—and avoidance of removing healthy tissue—continues to be a challenge. Current imaging techniques are said to not be sensitive enough to always recognize between benign and malignant tumors. The new technique uses clinically approved fluorescent dye that’s comparable with standard cameras used in operating theaters around the world.
 

Baran Sumer, M.D.
Division Chief, University of Texas Southwestern Medical Center

"We were able to invent a nanoprobe, which when injected intravenously into mice with tumors, specifically targets the cancer and turns on, illuminating them. The illumination is fluorescence but the switch-like on/off behavior of the nanoprobes is what is unique," co-author Baran Sumer, a surgeon at the University of Texas Southwestern Medical Center told R&D Magazine in an exclusive interview. "It turns out that human cancers are slightly more acidic than normal tissue and this is what we are taking advantage of. When the nanoprobes detect this acidic tumor environment, they turn on." 

Tumor acidity arises from increased metabolism of tumor cells to take up glucose and make lactic acids, a process known as Warburg effect back in the 1920’s by a Nobel Laureate, Otto Warburg.  Clinically, the Warburg effect has been widely validated in human patients by the use of 18FGD, a glucose analog, to detect malignant tumors by positron emission tomography due to elevated 18FDG uptake, said Prof. Jinming Gao, also of UT Southwestern, the other senior author of the paper, to R&D Magazine.

Similar to a transistor, which switches on when voltage rises above a given threshold, the nanoprobes light up only in the presence of acidic pH. When used to take off tumors from head and neck of mice, the physicians found the devices gave them “unprecedented specificity and sensitivity.” These synthetic probes lit up tumor nodules less than 1 millimeter in diameter.

“Molecular imaging of cancer-specific biomarkers offers the exciting opportunity for tumor detection at the earliest onset of disease and has rapidly advanced the preclinical and clinical development of a variety of imaging probes,” per the study.

Prior, something like this was not possible with the same degree of precision because the on/off switching behavior is unique to nanoscale technology, which is measured in billionths of meters.

"One advantage of this is that the nanoprobes work in almost all cancers since the acidic environment is a universal feature of cancer. This is also the case in human cancers and therefore we anticipate the nanoprobes will work in a similar fashion for human cancers as well, "Sumer told R&D. "We believe this will also work in humans and human studies are planned in early to mid 2017." 

This photo shows a Schematic of pH nanotransistor with binary off/on response at a pHt (threshold pH for fluorescence transition) of 6.9. At pH < 6.9, nanoprobes dissociate into protonated, highly fluorescent unimers (on state); at pH > 6.9, nanoprobes are silent (off state). b, PINS nanoprobes (intravenous injection given 24 hours prior to imaging by SPY Elite clinical camera) demonstrate broad tumor imaging efficacy in a variety of tumor models (head and neck, breast, peritoneal metastasis, kidney, brain, pancreatic) and organ sites. (Credit: Nature Biomedical Engineering)
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