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Contrast agents improve fluorescence-guided surgery

Scaffold that requires multiple protein-cleaving enzymes activates signal specifically in tumors

by Celia Henry Arnaud
October 3, 2020 | A version of this story appeared in Volume 98, Issue 38


Cartoon showing AND-gate contrast agents with a fluorescent dye and two quenchers.
Credit: Nat. Biomed. Eng.
AND-gate contrast agents contain a fluorescent dye and two quenchers attached to a peptide scaffold. Each arm of the scaffold contains a cleavage site for a different protease. Fluorescence is activated only after both quenchers have been released.

Fluorescent contrast agents can help identify the locations of tumors during surgery, but the contrast between tumors and healthy tissues can be reduced if a dye doesn’t specifically target a tumor. Researchers led by Matthew Bogyo of Stanford University report that they have developed new agents that boost fluorescence contrast in tumors by turning on only when two tumor-specific protein-cleaving enzymes are present (Nat. Biomed. Eng. 2020, DOI: 10.1038/s41551-020-00616-6). The so-called AND-gate contrast agents consist of a peptide scaffold with a fluorescent dye attached to a central portion and two quencher molecules attached to two arms. Each arm contains a cleavage site for a different tumor-specific enzyme. Fluorescence is activated only if both quenchers are removed, which requires both enzymes to be present and lessens the likelihood of observing a signal in healthy tissue. The researchers altered the selectivity of the contrast agents by incorporating different enzyme cleavage sites in the scaffold. They used the imaging contrast agent for fluorescence-guided robotic surgery to remove mammary tumors and metastatic lung tumors in mice. After excision, the contrast agent revealed residual cancer cells that couldn’t be seen with conventional white-light imaging.


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