Abstract
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.
Highlights
Chemodynamic therapy (CDT) is an emerging cancer treatment, which depends on the Fenton or Fenton-like reactions to obtain highly toxic hydroxyl radicals (·OH)
Cu-based nanotherapeutic agents for chemodynamic therapy (CDT) have attracted a lot of attention
The pH values show a time-dependent mode and a concentration-dependent mode (Glu). These results indicate that GOD loaded in
Summary
Chemodynamic therapy (CDT) is an emerging cancer treatment, which depends on the Fenton or Fenton-like reactions to obtain highly toxic hydroxyl radicals (·OH)for killing cancer cells [1]. Chemodynamic therapy (CDT) is an emerging cancer treatment, which depends on the Fenton or Fenton-like reactions to obtain highly toxic hydroxyl radicals (·OH). The tumor microenvironment is characterized by overexpression of H2 O2 , glutathione (GSH) and weak acidity [7,8]. The Fe-based Fenton reaction is only effective under strongly acidic conditions (pH 2–4) [10]. The Fentonreaction of Fe will be limited under the neutral and weakly acidic microenvironment conditions encountered in tumors. Mn(II) used in Fenton-like reactions only remains stable when pH < 4. A large amount of GSH in tumor cells can react with reactive oxygen species and affect the concentration of H2 O2 and ·OH. Cu-based nanotherapeutic agents for CDT have attracted a lot of attention
Sign-in/Register to view highlights & summary Sign-in/Register to access full text options 
Free) 
Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Schedule a call
