Targeted Chemotherapy Using in Vivo Transition Metal Catalysis

Key words

quinoline synthesis - gemcitabine - affibody - catalytic chemotherapy

Significance

The human epidermal growth factor receptor 2 (HER2) is overexpressed in many cancer cell lines. The authors developed a ruthenium-containing affibody, Ru-HER2, with a dual mechanism of action. It selectively binds and blocks HER2, and locally activates a gemcitabine prodrug, resulting in high anticancer activities with reduced cytotoxicity for healthy cells.

Comment

The ruthenium-containing intermediate Ru-MI was coupled to a HER2 affibody in a 1:1 ratio using maleimide thiol chemistry. This construct was capable of uncaging allyloxy carbamateprotected gemcitabine in vitro and in vivo. The selective and controlled introduction of DNA damage caused by the uncaged gemcitabine in cancer cells opens a new strategy for catalytic chemotherapy.

Publication History

Article published online:
18 July 2022