Copper peroxide coated upconversion nanoparticle modified with glucose oxidase for H2O2 self-supplying starvation-enhanced chemodynamic therapy in vitro

Abstract

Chemodynamic therapy (CDT) can convert endogenous hydrogen peroxide (H₂O₂) to highly reactive hydroxyl radical (˙OH) through Fenton or Fenton-like reaction to kill tumor cells, which is a promising anticancer strategy. However, the limited H₂O₂ and overexpressed glutathione (GSH) in tumor cells make CDT ineffective. Here, an efficient nanocomposite, UCN@CuO₂–GOx (UCCuG), was synthesized, realizing both starvation therapy and H₂O₂ self-supplying CDT in vitro. In this case, the glucose oxidase (GOx) of the nanocomposite could consume glucose for starvation therapy after the UCCuG nanocomposite entered tumor cells. In addition, the acidic environment of the lysosome triggered the release of Cu²⁺ and H₂O₂ by the decomposition of UCCu; then, Cu²⁺ was reduced to Cu⁺ by GSH in tumor cells; and finally, Cu⁺ catalyzed the released H₂O₂ to generate ˙OH for CDT. The in vitro experiments demonstrated starvation-enhanced CDT with remarkable results. Meanwhile, under 980 nm laser irradiation, the upconversion luminescence signal of UCN in the UCCuG nanocomposite was reduced due to the CuO₂–GOx coating, while it gradually recovered after the UCCuG nanocomposite reacted with glucose and GSH under the tumor microenvironment (TME). Such a luminescent intensity recovery process is expected to monitor the TME-activated therapeutic effect in real time. This strategy may solve the problem of insufficient CDT efficacy caused by limited endogenous H₂O₂ and overexpressed GSH in tumor cells. This multifunctional nanocomposite demonstrates the promising application of starvation-enhanced CDT in tumor treatment.