Jing Xia MSc , Guoxin Liu PhD , Chaofan Wang MSc , Zhuo Liu MSc , Fengyu Liu PhD , Hongjuan Li PhD , Yongqian Xu PhD , Shiguo Sun PhD
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引用次数: 0
Abstract
Disulfiram (DSF), as a sixpenny drug for the treatment of alcohol dependence, has demonstrated copper-dependent chemotherapy (CT) effects in recent years. However, as the most common modality in clinical treatment, prolonged use of CT will lead to multidrug resistance (MDR). In this work, a versatile and ingenious nanoparticle Cu/ZIF-8@DSF@GOx/HA (CZDGH) was constructed to deliver DSF, Cu2+ and GOx to tumor cells. Once internalized by tumor cells, GOx depletes glucose blocking the energy supply leading to ST. Then DSF chelates with Cu2+ in situ to generate CuETs, achieving toxicity-intensified CT, the reduced ATP in this process also inhibits the efflux function of P-gp. In the meantime, Cu2+ consumes glutathione (GSH) to enhance oxidative stress, and the converted Cu+ catalyzes internal and external sources of H2O2 into •OH, heightening chemodynamic therapy (CDT). The experimental results demonstrate remarkable multimodal synergistic anticancer effects that overcome MDR.
期刊介绍:
The mission of Nanomedicine: Nanotechnology, Biology, and Medicine (Nanomedicine: NBM) is to promote the emerging interdisciplinary field of nanomedicine.
Nanomedicine: NBM is an international, peer-reviewed journal presenting novel, significant, and interdisciplinary theoretical and experimental results related to nanoscience and nanotechnology in the life and health sciences. Content includes basic, translational, and clinical research addressing diagnosis, treatment, monitoring, prediction, and prevention of diseases.