Atom engineering-regulated in situ transition of Cu(Ⅰ)-Cu(Ⅱ)for efficiently overcoming cancer drug resistance

The search of highly efficient drugs for overcoming cancer drug resistance continues to be a challenge for scientists.Constructing a metal drug based in situ oxidation-state transition system to disturb the redox balance in cancer cells is a promising approach for overcoming cancer drug resistance.Inspired by natural redox-active copper enzyme centers,we developed a Cu(Ⅰ)-Cu(Ⅱ) in situ transition system in this work.Through atom engineering,we fine-tuned the thermodynamic stability of this system to investigate its anticancer activity.The results indicated that the synthetic Cu(Ⅰ)-Cu(Ⅱ) system could under-go in situ transition in vitro and in vivo,to disrupt the intracellular redox balance and trigger mitochondrial dysfunction and G2/M arrest,leading to apoptosis and overcoming cancer drug resistance.This study presents a feasible way to overcome cancer drug resistance by designing an in situ oxidation-state transition metal drug system.