Cu-Ferrocene-Functionalized CaO₂ Nanoparticles to Enable Tumor-Specific Synergistic Therapy with GSH Depletion and...

The conversion of endogenous H₂ O₂ into toxic hydroxyl radical (^• OH) via catalytic nanoparticles is explored for tumor therapy and received considerable success. The intrinsic characteristics of microenvironment in tumor cells, such as limited H₂ O₂ and overexpressed glutathione (GSH), hinder the intracellular ^• OH accumulation and thus weaken therapeutic efficacy considerably. In this study, fine CaO₂ nanoparticles with Cu-ferrocene molecules at the surface (CaO₂ /Cu-ferrocene) are successfully designed and synthesized. Under an acidic condition, the particles release Ca²⁺ ions and H₂ O₂ in a rapid fashion, while they can remain stable in neutral. In addition, agitated production of ^• OH occurs following the Fenton reaction of H₂ O₂ and ferrocene molecules, and GSH is consumed by Cu²⁺ ions to avoid the potential ^• OH consumption. More interestingly, in addition to the exogenous Ca²⁺ released by the particles, the enhanced ^• OH production facilitates intracellular calcium accumulation by regulating Ca²⁺ channels and pumps of tumor cells. It turns out that promoted ^• OH induction and intracellular calcium overload enable significant in vitro and in vivo antitumor phenomena.