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

The conversion of endogenous H2O2 into toxic hydroxyl radical ((OH)-O-center dot) via catalytic nanoparticles is explored for tumor therapy and received considerable success. The intrinsic characteristics of microenvironment in tumor cells, such as limited H2O2 and overexpressed glutathione (GSH), hinder the intracellular (OH)-O-center dot 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 H2O2 in a rapid fashion, while they can remain stable in neutral. In addition, agitated production of (OH)-O-center dot occurs following the Fenton reaction of H2O2 and ferrocene molecules, and GSH is consumed by Cu2+ ions to avoid the potential (OH)-O-center dot consumption. More interestingly, in addition to the exogenous Ca2+ released by the particles, the enhanced (OH)-O-center dot production facilitates intracellular calcium accumulation by regulating Ca2+ channels and pumps of tumor cells. It turns out that promoted (OH)-O-center dot induction and intracellular calcium overload enable significant in vitro and in vivo antitumor phenomena.

Automated summary

The study successfully designed and synthesized fine CaO2 nanoparticles with Cu-ferrocene molecules on the surface, which release Ca2+ ions and H2O2 under acidic conditions and promote the production of (OH)-O-center dot. The enhanced (OH)-O-center dot induction and intracellular calcium overload contribute significantly to antitumor effects in vitro and in vivo.