Perturbing tumor cell metabolism with a Ru(II) photo-redox catalyst to reverse the multidrug resistance of lung cancer

Abstract

The novel concept of enzyme photocatalysis has recently attracted much attention in developing anticancer therapy. However, the relationship between coenzyme depletion and cellular metabolomic changes has rarely been investigated. Herein, we report the rational design of a deep-red light-triggered bis-tridentate Ru(II) photocatalyst (Ru3), which induces cell metabolism disorder to combat multidrug resistance. Ru3 exhibits promising multiple triplet excited states, a long lifetime, and high photocatalytic activity toward the coenzyme. Consequently, Ru3 shows high phototherapeutic activity (photo index = 191–833) against diverse resistant (cisplatin, 5-fluorouracil, or paclitaxel) lung cancer cells by inhibiting cellular peptide, lipid, and glycerophospholipid metabolism. We believe that cell metabolism inhibition by photo-redox catalysts is an effective form of therapeutics for drug-resistant cancer cells. [Figure not available: see fulltext.] © 2023, Science China Press.