Fenton-like reaction performing mineralized nanocarriers as oxidative stress amplifying anticancer agents

Abstract We developed Fenton-like reaction performing mineralized nanoparticles as novel oxidative stress amplifying anticancer agents. We fabricated Cu-doped superoxide dismutase (SOD)-loaded calcium carbonate (CaCO3)-mineralized nanoparticles (Cu/SOD-MNPs) that could simultaneously release hydrogen peroxide-generating SOD and Fenton-like reaction-inducing copper ions within cancer cells. The CaCO3 core of the Cu/SOD-MNPs effectively inhibited the release of the entrapped SOD and copper ions in physiological pH (7.4). In contrast, in acidic pH (5.0), the release of SOD and copper ions was facilitated by CaCO3 dissolution. We demonstrated that the Cu/SOD-MNPs elevated the level of highly toxic apoptosis-inducing hydroxyl radicals in the cancer cells. The Cu/SOD-MNPs showed specific toxicity for cancer cells (MCF-7 cells), whereas no or negligible toxicity was found for normal cells (NIH3T3 and HEK293 cells). This mineralized oxidative stress amplifying nanoparticle may serve as a novel cancer-specific anticancer agent.