Oxidative stress induced by reactive oxygen species (ROS) is one of the critical factors that involves in the pathogenesis and progression of many diseases. However, lack of proper techniques to scavenge ROS depending on their cellular localization limits a thorough understanding of the pathological effects of ROS. Here, we demonstrate the selective scavenging of mitochondrial, intracellular, and extracellular ROS using three different types of ceria nanoparticles (NPs), and its application to treat Parkinson's disease (PD). Our data show that scavenging intracellular or mitochondrial ROS inhibits the microglial activation and lipid peroxidation, while protecting the tyrosine hydroxylase (TH) in the striata of PD model mice. These results indicate the essential roles of intracellular and mitochondrial ROS in the progression of PD. We anticipate that our ceria NP systems will serve as a useful tool for elucidating the functions of various ROS in diseases.

An urgent need in chemodynamic therapy (CDT) is to achieve high Fenton catalytic efficiency at small doses of CDT agents. However, simple general promotion of the Fenton reaction increases the risk of damaging normal cells along with the cancer cells. Therefore, a tailored strategy to selectively enhance the Fenton reactivity in tumors, for example, by taking advantage of the characteristics of the tumor microenvironment (TME), is in high demand. Herein, a heterogeneous CDT system based on copper−iron peroxide nanoparticles (CFp NPs) is designed for TME-mediated synergistic therapy. CFp NPs degrade under the mildly acidic conditions of TME, selfsupply H 2 O 2 , and the released Cu and Fe ions, with their larger portions at lower oxidation states, cooperatively facilitate hydroxyl radical production through a highly efficient catalytic loop to achieve an excellent tumor therapeutic efficacy. This is distinct from previous heterogeneous CDT systems in that the synergism is closely coupled with the Cu + -assisted conversion of Fe 3+ to Fe 2+ rather than their independent actions. As a result, almost complete ablation of tumors at a minimal treatment dose is demonstrated without the aid of any other therapeutic modality. Furthermore, CFp NPs generate O 2 during the catalysis and exhibit a TME-responsive T 1 magnetic resonance imaging contrast enhancement, which are useful for alleviating hypoxia and in vivo monitoring of tumors, respectively.

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