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.