Scientists develop ‘smart’ molecules to target cancer cells

The research was conducted in collaboration with colleagues from the Institute of Organic Chemistry of the Russian Academy of Sciences and Aix-Marseille University in France. The findings were published in the journal Chemical Research in Toxicology.

A prodrug is a molecule that does not become active immediately but is instead designed to be activated inside cancer cells, where it can trigger a series of reactions intended to destroy the tumor.

The new approach is based on compounds known as alkoxyamines—powerful substances that are generally not selective in their effects. Researchers developed a strategy to effectively “mask” these compounds so that they can be activated only under specific conditions.

An enzyme known as beta-galactosidase, which is found in high concentrations in cancer cells, cuts through the sugar-based protective component, releasing the active molecule through a self-immolative linker.

Tests showed that the newly developed compounds suppressed tumor growth more effectively than cisplatin, one of the most widely used chemotherapy drugs.

Tests Across Different Cancer Cell Types

The researchers tested the compounds on prostate adenocarcinoma, ovarian adenocarcinoma, breast adenocarcinoma and T-cell lymphoblastic leukemia cells, as well as a mouse embryonic fibroblast cell line.

The results showed that free alkoxyamines were toxic to cells even at relatively low concentrations.

By contrast, compounds linked to galactose through a stable linker displayed significantly weaker activity, requiring concentrations four to five times higher to achieve the same effect. According to the researchers, this was because although the enzyme was able to remove the sugar component, it could not release the active alkoxyamine.

Compounds containing self-immolative linkers, however, significantly suppressed the growth of cancer cells. In some cases, they required lower concentrations than cisplatin to reduce the viability of cancer cells.

A Long Road Ahead Before a Clinical Drug

One of the study's authors, Pavel Pytonin, an associate professor at the School of Chemical and Biomedical Technologies at Tomsk Polytechnic University, stressed that the research remains at an early stage.

“The drug is still in its preliminary stages, and we are not talking about a finished medicine,” he said. “It is necessary to study its mechanism of action and the behavior of these compounds in living systems in greater detail.”

He added that one of the key challenges is ensuring that the compounds selectively target cancer cells without damaging healthy cells.

“Nevertheless, we can currently assume that this modular structure could eventually allow researchers to modify the sugar component, the linker and the active component, making it possible to adapt the drug for different types of cancer cells,” he said.

The findings could provide a foundation for the development of more precise cancer treatments, although further research will be needed to determine how the compounds behave in living organisms and whether they can be developed into safe and effective therapies for patients.