Glucose oxidase loaded Cu based metal-organic framework for glutathione depletion/reactive oxygen species elevation enhanced chemotherapy.

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

Methods: Here in our study, a Cu 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.

Results: Our results showed that the GOx can catalyze glucose and produce HO. In the mean time, the Cu can react with GSH and then transform into Cu, which resulted in GSH depletion. Afterwards, the produced Cu and HO 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.

Discussion: 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.