05-Jun-2020 - University of Notre Dame

A molecular shield for near-infrared fluorescent dyes

Stable and Functional Dyes for Near-Infrared Fluorescence Imaging of Living Subjects

Scientists can monitor biomolecular processes in live tissue by noninvasive optical methods, such as fluorescence imaging. However, the fluorescent dyes used for that purpose are often rather unstable, and photobleaching, lack of specificity, and poor pharmacokinetics are recurrent issues. US scientists have developed a molecular shield that stabilizes near-infrared fluorescent dyes and enhances their functionality. Their synthesis and characterization are reported in the journal Angewandte Chemie.

Fluorescence bioimaging often uses the near-infrared light region because this radiation can efficiently penetrate human tissue. Fluorescent dyes designed for this purpose usually have a flat, symmetrical molecular architecture, which favors absorption of near-infrared light, but the dyes also need to be water soluble and carry functional groups for conjugating with targeting biomolecules, for example, antibodies or tumor-binding peptides. A member of this class of fluorescent dyes, called heptamethine cyanines, or Cy7, is currently under investigation in surgical applications.

However, the Cy7 molecules have their drawbacks. Their light-absorbing chromophore is vulnerable to oxygen radicals, which leads to bleaching. In addition, the flat rigid molecules may aggregate and interact nonspecifically with other biomolecules, which slows down their clearance from the body.

To tackle these issues, Bradley D. Smith and his group at the University of Notre Dame, USA, improved the chemical structure of the dye. To protect the heptamethine chromophore from oxygen attack, they introduced a voluminous and smart shield. They attached a bulky aromatic group on top of the central part of the chromophore and furnished this top group with long shielding arms projecting over both faces of the chromophore, like a bird covering its nest with its wings.

The resulting dye, which the scientists call “sterically shielded heptamethine cyanine dye” or s775z, was water soluble and provided stable fluorescence. The shielded architecture prevented aggregation and photobleaching, the authors reported. The dye was exceptionally stable against chemical degradation and could be stored “indefinitely” in a common refrigerator, the authors wrote.

They also performed imaging studies in live mice and found that s775z, in contrast to all other studied dyes, did not accumulate in the blood clearance organs, but was washed out of the body quickly. Moreover, a cancer-targeted version of s775z accumulated at a high level in tumors and could be visualized by fluorescence imaging of the live mice.

The authors suggest that the new s775z dye will be useful for a wide range of biomedical imaging applications. They point out that the change from a flat molecule to a three-dimensional shielding architecture was the key to make this class of near-infrared fluorescence dyes more stable and efficient.

University of Notre Dame

Recommend news PDF version / Print

Share on

Facts, background information, dossiers
More about University of Notre Dame
  • News

    Engineers develop prototype of electronic nose

    There’s nothing like the smell of freshly brewed coffee in the morning. But how does one measure that smell? There’s no energy in a smell to help estimate how potent the coffee might be. Instead, it’s the gases emitted from brewed coffee that contribute to the invigorating scent. The human ... more

    Shedding new light on influenza detection

    Researchers at the University of Notre Dame have discovered a way to make influenza visible to the naked eye, according to a new study. By engineering dye molecules to target a specific enzyme of the virus, the team was able to develop a test kit that emitted fluorescent light when illumina ... more

    Researchers track perfluorinated chemicals in the body

    They are the chemicals that made consumers think twice about using nonstick cookware. New research shows scientists have developed a method to track perfluorinated alkyl substances (PFAS) in the body. PFAS are potentially toxic chemicals found in stain-resistant products, nonstick cookware, ... more

More about Angewandte Chemie
  • News

    Cellular Communication Agent

    Both nitric oxide (NO) and hydrogen sulfide (H2S) act as gaseous signaling molecules with similar physiological effects. Many of the critical questions about the interplay between these two gasotransmitters hinge on their chemical reactivity and the fleeting existence of HSNO, a key product ... more

    Overcoming False Optical Activity

    Many natural products are complicated organic molecules. Despite this complexity, scientists are usually able to investigate them using spectroscopic techniques. However, a team of researchers has now discovered that care should be taken using Raman spectroscopy to analyze certain chiral mo ... more

    Electrons Passed Around

    Photoinduced charge transfers are an interesting electronic property of Prussian blue and some analogously structured compounds. A team of researchers has now been able to elucidate the ultrafast processes in the light-induced charge transfer between iron and manganese in a manganese-contai ... more