The guiding light

Oregon State’s ‘glowing’ nanotechnology guides cancer surgery, zaps remaining malignant cells

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CORVALLIS, Ore.—Targeted toward improving the outcome of cancer surgery, researchers at Oregon State University (OSU) have developed and launched a new tumor-seeking weapon to theoretically extinguish all malignant cancer cells by selectively inserting compounds into the cancer cells, thus allowing surgeons to identify malignant tissues. Then, in combination with phototherapy, the tumor will not only be removed, but the innovative method will kill any remaining cancer cells, both through mild heating and generating reactive oxygen species.
 
This procedure may one day answer, at least for some, the age-old lingering question: Doc, did you get it all?
 
“It’s about as simple as, ‘If it glows, cut it out,’ David Stauth, science writer at OSU, stated in a recent news release. “And if a few malignant cells remain, they’ll soon die.”
 
The findings, published in the journal Nanoscale, have shown remarkable success in laboratory animals, Stauth said. The concept should allow more accurate surgical removal of solid tumors at the same time as it eradicates any remaining cancer cells. In laboratory tests, it completely prevented cancer recurrence in mice after phototherapy.
 
“This is kind of a double attack that could significantly improve the success of cancer surgeries,” says Oleh Taratula, an assistant professor in OSU’s College of Pharmacy. “With this approach, cancerous cells and tumors will literally glow and fluoresce when exposed to near-infrared light, giving the surgeon a precise guide about what to remove. That same light will activate compounds in the cancer cells that will kill any malignant cells that remain. It’s an exciting new approach to help surgery succeed.”
 
This research was done with ovarian cancer cells. Ovarian cancer is the deadliest of all cancers affecting the female reproductive system, with very few effective treatments available, according to the National Institutes of Health (NIH)
 
The work is based on the use of a known compound called naphthalocyanine, which, when exposed to near-infrared light, can make a cell glow to guide the surgeon, OSU researchers stated.
 
However, naphthalocyanine isn’t water-soluble, and also tends to clump up, or aggregate, inside the body during the process, thus losing its ability to make cells glow and generate reactive oxygen species. This also makes it difficult or impossible for it to find its way through the circulatory system and take up residence only in cancer cells.
 
OSU experts overcame these problems by use of a special water-soluble polymer, called a dendrimer, which allows the napthalocyanine to hide within a molecule that will attach specifically to cancer cells, Stauth said. The dendrimer, an extremely tiny nanoparticle, takes advantage of certain physical characteristics that blood vessels leading to cancer cells have, but healthy ones do not. It will slip easily into a tumor, but largely spare any healthy tissue.
 
This “one-two punch of surgery and a nontoxic, combinatorial phototherapy holds significant promise,” Taratula says. “It’s quite different from existing chemotherapies and radiotherapies.” He adds that this process “could someday eliminate—or at least reduce—the need for chemotherapy and radiation. For many cancers, surgery is a first choice of treatment. In coming years, we may have a tool to make that surgery more precise, effective and thorough than it’s been before.”
 
“Our findings highlight substantial progress in employing a single-agent-based nanomedicine platform capable of both NIR fluorescence imaging and anticancer therapy (combinatorial phototherapy in this case) with the near future prospective to detect and eradicate unresected cancer cells intraoperatively,” Taratula continues. “What we have learned from these studies is that it is possible to visualize and destroy cancer cells with a single agent, minimizing the cost, time and toxicity of intraoperative anticancer therapy.”
 
In order to get FDA approval for clinical trials with humans, the convincing therapeutical and safety results in animals have to be obtained, Taratula notes. “At the moment, we are continuing complete evaluation of this modality in mice. However, we are getting ready to test this system on dogs in collaboration with the Oregon State College of Veterinary Medicine.”
 
Systems with technology similar to this are also being tested by other researchers, but some of them require several imaging and therapeutic agents, repeated irradiation and two lasers, OSU researchers stated. This increases cost and may lessen effectiveness and increase the risk of side effects.
 
This nanotechnology work was initially supported by OSU College of Pharmacy.
 
“Recently, we received $120,861 from Venture Funds OSU to optimize the developed nanomedicine platform and complete critical animal studies, including detailed efficacy and toxicity, to advance this technology,” Taratula said. “Earlier, in 2013, $40,000 from the Medical Research Foundation of Oregon also supported initial work for this project.”
 
With cuts in grants from major learning institutions nationwide, funding for the future might be more difficult to obtain.
 
“At the moment, we have submitted one proposal to the NIH  and are working on other proposals to be submitted to NIH and other funding agencies like the American Cancer Society or Department of Defense,” Taratula says.
 
“However, according to our experience the funding situation remains tough with this project,” he added. “Therefore, we cannot predict how much money in grants funding could be received, if anything.”
 


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