Construction of novel nanocomposites (Cu-mof/god@ha) for chemodynamic therapy

The emerging chemodynamic therapy (CDT) has received an extensive attention in recent years. However, the efficiency of CDT is influenced due to the limitation of H₂O₂ in tumor. In this study, we designed and synthesized a novel core-shell nanostructure, Cu-metal organic framework (Cu-MOF)/glucose oxidase (GOD)@hyaluronic acid (HA) (Cu-MOF/GOD@HA) for the purpose of improving CDT efficacy by increasing H₂O₂ concentration and cancer cell targeting. In this design, Cu-MOF act as a CDT agent and GOD carrier. Cu(II) in Cu-MOF are reduced to Cu(I) by GSH to obtain Cu(I)-MOF while GSH is depleted. The depletion of GSH reinforces the concentration of H₂O₂ in tumor to improve the efficiency of CDT. The resultant Cu(I)-MOF catalyze H₂O₂ to generate hydroxyl radicals (·OH) for CDT. GOD can catalyze glucose (Glu) to supply H₂O₂ for CDT enhancement. HA act as a targeting molecule to improve the targeting ability of Cu-MOF/GOD@HA to the tumor cells. In addition, after loading with GOD and coating with HA, the proportion of Cu(I) in Cu-MOF/GOD@HA is increased compared with the proportion of Cu(I) in Cu-MOF. This phenomenon may shorten the reactive time from Cu-MOF to Cu(I)-MOF. The CDT enhancement as a result of GOD and HA effects in Cu-MOF/GOD@HA was evidenced by in vitro cell and in vivo animal studies.