Scientists from Trinity College Dublin have uncovered a new class of compounds glyconaphthalimides that can be used to target cancer cells with greater specificity than current options allow. The study was published in the journal Chemical Communications.
Cervical cancer cells show green fluorescence from enzyme-activated compound.
Credit: Eoin Scanlan, Trinity College Dublin.
Cancer is difficult to treat, and many current therapies are unable to specifically target cancer cells. This is problematic for medical professionals and patients, because it limits the dose of the drug that can be safely administered, and often causes severe and debilitating side-effects.
But the Trinity scientists have now demonstrated that a class of naturally occurring enzymes glycosidases that are heavily overexpressed in tumor tissue can be used to trigger the release of therapeutic payloads only in the local tumor sites where they are needed.
This finding may therefore result in the development of improved targeted cancer therapies with significantly reduced side-effects for patients.
In addition to killing cancer cells, the technology may also be used to image cancer cells, with potential applications in cancer imaging and diagnosis.
Associate Professor in Chemistry at Trinity, Eoin Scanlan, led the multidisciplinary group. He said: “This is a really exciting discovery because it brings us closer to more targeted treatment of cancer. Some current therapies are limited due to the toxicity of the compounds, but our compounds are completely inactive until they are released by the enzymes that are naturally overexpressed at the tumour site. The active compound is then rapidly taken up by cancer cells.”
“Our next steps will be to apply this technology to release specific anti-cancer drugs and to test it against a range of different cancer types.”
Citation: Calatrava-Pérez, Elena, Sandra A. Bright, Stefan Achermann, Claire Moylan, Mathias O. Senge, Emma B. Veale, D. Clive Williams, Thorfinnur Gunnlaugsson, and Eoin M. Scanlan. “Glycosidase activated release of fluorescent 1, 8-naphthalimide probes for tumor cell imaging from glycosylated ‘pro-probes’.” Chemical Communications 52, no. 89 (2016): 13086-13089.
Research funding: Science Foundation Ireland.
Adapted from press release by Trinity College Dublin.