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Rutgers, Singapore University Developing Nano-Surveillance Technology for Cancer Metastases

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NEW YORK (360Dx) – Researchers at Rutgers University and Singapore University of Technology and Design are working together to develop a diagnostic technique that obtains shortwave infrared signals that identify and trace the evolution of cancer cells inside the body.

The technique uses nanoparticles, or inks, tagged with antibodies, peptides, or drug molecules that have an affinity for cancer cells.

It could eventually complement some in vitro diagnostics used for cancer detection in clinical use, but it interrogates cells while they are inside the body based on the infrared signals emitted by protein-encapsulated, rare-earth phosphorus particles, said Prabhas Moghe, one of the technique's developers, in an interview. Moghe is a distinguished professor of biomedical, chemical, and biochemical engineering at Rutgers.

The team has plans to develop a commercial diagnostic system that could be available within about five years to guide surgeons looking to conduct more precise and less invasive surgeries on cancerous cells than is now possible, he said.

Most in vivo imaging methods, including those that use computerized tomography (CT) and magnetic resonance imaging (MRI), fail to detect small cancerous lesions, the researchers said in a study describing their work, published online on Tuesday in Nature Biomedical Engineering.

In their study, the researchers experimented with mice to show that albumin-encapsulated nanoparticles injected intravenously emitted shortwave infrared light and detected targeted metastatic lesions in vivo. In a murine model of human breast cancer, they said, the nanoprobes that they developed enabled whole-body detection of adrenal-gland microlesions three weeks after inoculation that were undetectable by contrast-enhanced magnetic resonance imaging. The nanoprobes detected bone lesions, also undetectable by MRI, five weeks after inoculation.

Julia Tchou, a breast cancer surgeon at Penn Medicine who was not involved in development of the nanoparticle technology, said in an interview that the research published in the study could lead to a breakthrough for cancer surgeons because of its potential to enable a clearer view of microscopic cancer cells. 

"Most of my surgeries are lumpectomies to remove cancer, and quite often the patient and the patient's family will ask if I have removed all of the cancer cells," she said. "I am usually stumped when they ask me the question. I have to say that I can't be sure. It's easy for me to remove the main tumor, but I cannot see the microscopic tumor foci that are often in the lumpectomy bed."

That means that up on up to 50 percent of women cannot be sure that all the cancerous cells have been cleared, Tchou noted.

"Many of these women will need a second surgery to clean the margin," Tchou said, adding, "It creates anxiety, uncertainty, and potential morbidity related to the second surgery. This new technology could be applied so that we can see and remove what's in the lumpectomy bed at the time of surgery."

Moghe noted that the technique has other potential implications. Its ability to detect ongoing changes as cancer spreads in the body has implications not only for its diagnosis and for guiding more precise surgeries, but also for tracking the body's response to cancer treatments, he said.

"In this paper, we followed these cells after they had been inoculated, and after a few weeks they started to spread," Moghe said, adding, "They metastasized to two different regions. One was to the long bones of the animals, a process that replicates what happens in humans, because one of the really important metastatic sites for human breast cancer is the long bones."

Another important advance was being able to track the same cancer cells as they travel to different sites in the body, including the adrenal glands, he said.

"The primary cancer can be taken out by a surgeon, but it is often the spread of cancer that introduces the risk of mortality," he noted.

Both Moghe and Tchou, who expects to be involved in the mouse-to-human translation, said that they believe that replicating the work in humans should not only be possible, but be relatively easy.

Getting regulatory approval for the system could prove to be more challenging, Moghe said, but he noted that his group is putting together a commercial plan and talking to investors, and clinical and regulatory advisors.

Investors should be interested in the "platform" nature of the technology — that it can be applied not only to several cancers but also in a few different ways. Use of the technique as a clinical diagnostic test to guide surgeries for cancers in humans is the ultimate objective, but the method could first be applied in a preclinical setting to conduct research into the detection and behavior of human cancer cells injected into animals. By exploring this preclinical pathway, the team could also apply the technique to detect cancers in animals, he noted, adding that this would be an easier regulatory path. 

The technique, in part because it involves injecting nanoinks encapsulated in proteins into the body, falls in a gray zone between drug, diagnostic, and device, he noted. However, he said that the research team is working to develop an optimal path to commercialization and that it was considering several options, including the assembly of several teams, each dedicated to working on a different commercial path.

Moghe said he sees the technique complementing other advanced diagnostics and biotech tools, including molecular and genetic tests being developed and commercialized for the early detection of cancers.

"In our in vivo biopsies, we are imaging cells inside the body, but our contrast agents could be complementary to other tests used in cancer detection," he said. He noted that the research team is also developing methods of transporting genes to cells. "We are looking at informing about the presence of genetic markers as well as silencing or actuating genes," he said. "You can potentially exploit one range of the electromagnetic spectrum to do surveillance and others to implement the other cell manipulation processes."

The use of nanoparticles for cancer diagnostics is a "very active area" of research across the US and throughout the world, Moghe noted. To develop better diagnostics, researchers are using MRI and other optical imaging methods, such as the near-infrared and Raman spectroscopy, along with nanoparticles, he said. However, the research team is among the early adopters of the use of shortwave infrared light for in vivo diagnostics, he said.

"We're working in a relatively new optical window that is only beginning to be explored in medical and health science," he said, adding, "In this range of energies and frequencies, light penetrates easier and deeper into tissues than is possible by other diagnostic methods such as magnetic resonance imaging."

Most important, the nanoparticles are biocompatible and safe for the body, he said. "We encapsulate the nanoparticle with a protein and make it essentially invisible to the body," Moghe said. "The protein enables rapidly dispersing the nanoparticle throughout the body and allows its release a few days later." The team can trace the quantity of nanoparticles entering and being expelled from the body to make sure they match, he added.