Imaging agents turn on two cancer biomarkers at once to provide a more complete picture of the tumor

June 05, 2023

(Nanowerk News) Cancer surgeons may soon have a more complete picture of tumors during surgery thanks to new imaging agents that can beam multiple biomarkers at once, report University of Illinois Urbana-Champaign researchers. Fluorescent nanoparticles, encased in red blood cell membranes, target tumors better than currently approved clinically available dyes and can emit two different signals in response to just one beam of surgical light, a feature that can help clinicians differentiate tumor boundaries and identify metastatic cancer. .

The imaging agent could be combined with a bioinspired camera, previously developed by researchers for real-time diagnosis during surgery, said research group leader Viktor Gruev, an Illinois professor of electrical and computer engineering.

In a new study in the journal ACS nano (“Cell membrane-coated nanoparticles for tumor delineation and qualitative estimation of cancer biomarkers at single-wavelength excitation in murine and phantom models”), the researchers demonstrated their new dual-signal nanoparticle in a tumor phantom – a 3D model that mimics features of a tumor and its surroundings – and in live mice. Researcher Indrajit Srivastava holds a nanoparticle solution that can target two cancer biomarkers, giving off two different signals when illuminated by a single fluorescent wavelength. This can provide surgeons with a more complete picture of the tumor and guide operating room decisions. In the background is a microscopic scan of a tissue sample. (Image: Fred Zwicky)

“If you want to find all cancers, imaging one biomarker is not enough. It can miss some tumors. If you include a second or third biomarker, the probability of eliminating all the cancer cells increases, and the probability of a better outcome for the patient increases.” said Gruev, who is also a professor at Carle Illinois College of Medicine. “Multi-target drugs and imaging agents are a recent trend, and our group is pushing the trend hard because we have camera technology that can image multiple signals at once.”

Traditionally, a surgeon removes the tumor and sends it to a pathologist for assessment, a process that can take hours to days, said Illinois postdoctoral researcher Indrajit Srivastava, the paper’s first author. As research has moved toward real-time diagnostics, several challenges have prevented widespread application: Many tumor-targeting imaging agents only achieve their tumor target only minimally, instead of being rapidly cleared from the bloodstream and accumulating in the liver, Srivastava said.

“Several people before us have used nanoparticles coated with red blood cells and found that they circulate much longer – a few days. We saw the same thing in our mice: The membrane-coated nanoparticles circulate longer in the blood, with reduced absorption in the liver. As it circulates longer, more imaging agent accumulates in the tumor, giving us a stronger fluorescent signal,” said Srivastava. An artist’s rendering of membrane-enclosed nanoparticles that bind to a marker on a cancer cell and emit colored light.

The two biomarkers targeted by the new imaging agents include one that is prevalent in early-stage cancer and another that is prevalent in late-stage cancer, which is more likely to metastasize. The researchers found that the probe was effective in differentiating cancer tissue from healthy tissue, as well as differentiating the two signals from one another.

“This is interesting for surgical applications, as it can help determine exactly where to cut. Having multiple signals provides a more comprehensive picture of the tumor. And that can tell the surgeon, ‘This may be metastatic, you may want to be more aggressive in your removal.’” says Srivastava.

Requiring only one wavelength of laser light to acquire multiple signals is another benefit for surgical applications, as it makes instrumentation much more compact than requiring multiple lasers for each required wavelength, said Gruev.

The researchers plan to develop more tumor imaging agents that target multiple markers, and continue further preclinical and clinical studies using the dual signal dye with the surgical glasses they have developed.

“In this battle to ensure we remove all cancer cells during surgery, we need investments in both imaging camera technology and in tumor targeting agents,” said Gruev. “This work helps us become more aware of and guide the holistic approach we take as we move closer to clinical trials.”

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