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

Jinzhi Xu,Yan Xu,Lixin Sun,Bei Lu,Xi Yan,Zhonghao Wang,Tong Zhang

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 2+ 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 H 2 O 2 . In the mean time, the Cu 2+ can react with GSH and then transform into Cu + , which resulted in GSH depletion. Afterwards, the produced Cu + and H 2 O 2 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.