Bimetallic-organic framework for GSH depletion chemokinetic/ chemotherapy combination therapy

Chemodynamic therapy (CDT) holds great promise in the field of cancer treatment. However, the therapeutic effect is affected by overexpression of glutathione (GSH) in the tumor microenvironment. Here, a pH-sensitive bimetallic zeolite imidazole ester backbone (Cu/ZIF-67@5-FU) with GSH depletion, CDT enhancement, and chemotherapeutic agent 5-fluorouracil (5-FU) loading was constructed to enhance the tumor treatment effect. The nanocomposite is able to cleave and release Cu²⁺ and Co²⁺ in a weak acidic environment. Co²⁺ undergoes a Fenton-like reaction and decomposes H₂O₂ to produce toxic hydroxyl radicals (·OH), and GSH reduces Cu²⁺ to Cu⁺, further generating large amounts of reactive oxygen species, which results in the depletion of GSH and the enhancement of CDT in tumor cells, exhibiting pH sensitivity as well as catalytic activity of peroxidase-like enzymes, and achieved synergistic treatment with the 5-FU released together. The experimental results show that Cu/ZIF-67@5-FU, as a nanoscale chemodynamic therapy/chemotherapy synergistic treatment platform, significantly increas GSH depletion in a weakly acidic environment at pH=5.6, and demonstrat good cancer inhibition at a nanocomposite concentration of 100 μg/mL.