Prodrug design used to elicit tumor growth suppression

An international collaboration saw light in Nature Communications.

“It’s difficult to overestimate the importance of cancer research, since cancer is the second among causes of death globally,” comments co-author Igor Nasibullin. “In this paper, we tried to propose solutions to avoid side effects of chemotherapy.”

The research started with introducing a modified protein – artificial metalloenzyme. For a reaction to be localized in the tumor, the metal catalyst must selectively find ways to cancer cells. With the help of the metalloenzyme, the reaction could be induced in a live organism (mouse). The protein is infused with glycans, which allows to differentiate cancer cells from normal cells. As a result, selective accumulation of the metalloenzyme on the surface of the tumor was observed.

During the second stage, a prodrug activated by the metalloenzyme was introduced. The prodrug is catalyzed by the metalloenzyme in the tumor locations, thus producing an antitumor substance.

Mice were injected with HeLa tumor cells, which are often used for research purposes. The authors further plan to work with real tumors obtained from patients’ tissues.

The use of the catalytic system suppressed tumor growth and metastasizing, as well as decreased side effects. The results proved that cancer-stricken mice can be treated through drug synthesis inside their bodies.

Importantly, in January 2022, Kazan University prolonged its memorandum of understanding with RIKEN, the institution which served as a partner in this publication.

 

Synthetic prodrug design enables biocatalytic activation in mice to elicit tumor growth suppression

https://www.nature.com/articles/s41467-021-27804-5

 

Source text: Rufina Gimaletdinova

Translation: Yury Nurmeev