Glucose oxidase loaded Cu²⁺ based metal-organic framework for glutathione depletion/reactive oxygen species elevation...

The development of multidrug resistance (MDR) is a major cause for the failure of chemotherapy, which requires the aid of nanomedicine.

Here in our study, a Cu²⁺ based metal-organic framework (COF) was firstly developed and employed as a carrier for the delivery of glucose oxidase (GOx) and doxorubicin (Dox) (COF/GOx/Dox) for the therapy of MDR lung cancers.

Our results showed that the GOx can catalyze glucose and produce H₂O₂. In the mean time, the Cu²⁺ can react with GSH and then transform into Cu⁺, which resulted in GSH depletion. Afterwards, the produced Cu⁺ and H₂O₂ trigger Fenton reaction to generate ROS to damage the redox equilibrium of cancer cells. Both effects contributed to the reverse of MDR in A549/Dox cells and finally resulted in significantly enhanced in vitro/in vivo anticancer performance.

The combination of glutathione depletion/reactive oxygen species elevation might be a promising strategy to enhance the efficacy of chemotherapy and reverse MDR in cancers.