Selective Targeting of Cancer Cells Using an Artificial Metalloenzyme

In a study published today in Nature Catalysis, researchers present a promising method to deliver drugs selectively to cancer cells. The approach involves a clever combination of an artificial metalloenzyme that can protect its metal catalyst and a sugar chain “delivery tag.”

It has been difficult to use transition metal catalysts inside of organisms because they are easily quenched by substances like antioxidants. But the team developed an artificial metalloenzyme using a protein called human serum albumin, which is abundant in the human body. They introduced a ruthenium catalyst into the hydrophobic pocket inside the protein, which protected it from being quenched.

“We were pleasantly surprised that our newly developed metalloenzyme worked well in the presence of glutathione, an antioxidant that is abundant in actual cells and can inactivate ruthenium,” says senior author Katsunori Tanaka of RIKEN. “This told us that the ruthenium catalyst is well protected from hydrophilic components such as glutathione in the hydrophobic pocket of the albumin molecule, while hydrophobic compounds can come in contact with the catalyst within the pocket and undergo catalysis.”

Further, by attaching a sugar “delivery tag” to the surface of the artificial metalloenzyme, the researchers were able to target the metalloenzyme specifically to cancer cells. Once inside the cancer cells, the ruthenium was able to catalyze the production of an anti-cancer drug called umbelliprenin.

“We confirmed that the method we developed can be applied to metal-catalyzed reactions using other catalysts such as gold, and the artificial metalloenzyme could be generally used in vivo,” Tanaka adds. “If transition metal catalysis can be performed on specific organs or diseased cells in the body, it will allow us to rapidly and stably synthesize drugs there, minimizing side effects. Our findings could become a key in the fight against such diseases. Furthermore, we can consider using other natural compounds, which show strong anti-cancer activity but have not been used so far. We have opened a door to a new era where we can synthesize and activate natural chemical compounds in actual organisms.”