Jinzhi Xu1, Yan Xu2, Lixin Sun1, Bei Lu1, Xi Yan1, Zhonghao Wang1, Tong Zhang3. 1. Department of Thoracic Surgery, The Fourth Affiliated Hospital of Harbin Medical University, Harbin, China. 2. Department of Thoracic Surgery, The Fourth Affiliated Hospital of Harbin Medical University, Harbin, China. Electronic address: zhangtong_hmu60@163.com. 3. Department of Radiology, The Fourth Affiliated Hospital of Harbin Medical University, Harbin, China. Electronic address: zhangtong_hmu60@163.com.
Abstract
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 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. RESULTS: 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. 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.
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 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. RESULTS: 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. 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.