Fluorescence imaging has been a boon to research and medicine because of its ability to examine affected areas noninvasively. But the dyes used for these purposes have their disadvantages, and as resolution needs have grown stronger, the stakes for accuracy have increased exponentially.
A tumor-burdened mouse, imaged with the aid of s775z dye. Courtesy of Cynthia Schreiber.
A group of scientists from the University of Notre Dame has found that by creating a stable dye with a molecular shield — amounting to “arms” that prevent undesired binding with other dyes — they have been able to improve results over conventional alternatives. They used an aromatic compound to generate this effect and called this dye “sterically shielded heptamethine cyanine dye,” or s775z.
As researchers noted in their recent study, fluorescent heptamethine dyes allow for deep penetration of light in the NIR range of 740 to 840 nm. But in many cases there are drawbacks to their use in bioimaging, such as the likelihood they will bind with proteins and membranes away from a target, degrade chemically, and cause photobleaching.
“Our dye is both chemically stable and photochemically stable,” said researcher Cynthia Schreiber, who works in the lab of Bradley Smith, the director of the Notre Dame Integrated Imaging Facility. “By being chemically stable, our dye can be used in animal imaging experiments. By being photochemically stable, we can irradiate our dye with more photons, which is needed for several imaging techniques.”
The research paper describes the process of making a cyanine dye with the accompanying compound, and as a result of the process, the dye is charged to avoid binding, is water soluble, and provides stable fluorescence. This new dye, s775z, was tested in laboratory mice and was drawn to targeted areas, particularly cancer cells. Researchers also showed that it cleared easily from the bloodstream when the experiment was concluded and could also be easily refrigerated.
“Near-infrared dyes are inherently less stable than visible dyes where they need to be stored at a lower temperature and stored away from corrosive chemicals,” Schrieber said. “Compared to standard commercial dyes, our dye is very stable and, therefore, can be stored for long periods of time.”
Perhaps best of all, no toxicity was observed in the study subjects.
The research team determined that the high degree of stability in s775z makes it ideal for modern uses such as single-molecule tracking and superresolution imaging, and in medical applications such as fluorescence-guided surgery.
This research was published in Angewandte Chemie international edition (www.doi.org/10.1002/anie.202004449).