The mononuclear phagocyte system (MPS, e.g., liver and spleen) is often treated as a 'blackbox' by nano-researchers in translating nanomedicines. Often, most of the injected nanomaterials are sequestered by the MPS, preventing their delivery to the desired disease areas. Here, we exploit this imperfection by applying nano-antioxidants with preferential liver uptake to directly prevent hepatic ischemia-reperfusion injury (IRI), which is a reactive oxygen species (ROS)related disease. Ceria nanoparticles (NPs) were selected as a representative nano-antioxidant and detailed mechanism of preventing IRI was investigated. We found that ceria NPs effectively alleviated the clinical symptoms of hepatic IRI by scavenging ROS, inhibiting activation of Kupffer cells and monocyte/macrophage cells. The released pro-inflammatory cytokines were then significantly reduced and the recruitment and infiltration of neutrophils were minimized, which suppressed subsequent inflammatory reaction involved in the liver. The protective effect of nanoantioxidants against hepatic IRI in living animals and the revealed mechanism herein suggests their future use for the treatment of hepatic IRI in the clinic.

Acute kidney injury (AKI) is frequently associated with oxidative stress and causes high mortality annually in clinics. Nanotechnology‐mediated antioxidative therapy is emerging as a novel strategy for the treatment of AKI. Herein, a novel biomedical use of the endogenous biopolymer melanin as a theranostic natural antioxidant defense nanoplatform for AKI is reported. In this study, ultrasmall Mn2+‐chelated melanin (MMP) nanoparticles are easily prepared via a simple coordination and self‐assembly strategy, and further incorporated with polyethylene glycol (MMPP). In vitro experiments reveal the ability of MMPP nanoparticles to scavenge multiple toxic reactive oxygen species (ROS) and suppress ROS‐induced oxidative stress. Additionally, in vivo results from a murine AKI model demonstrate preferential renal uptake of MMPP nanoparticles and a subsequent robust antioxidative response with negligible side effects according to positron emission tomography/magnetic resonance (PET/MR) bimodal imaging and treatment assessment. These results indicate that the effectiveness of MMPP nanoparticles for treating AKI suggests the potential efficacy of melanin as a natural theranostic antioxidant nanoplatform for AKI, as well as other ROS‐related diseases.

The manifestation of acute kidney injury (AKI) is associated with poor patient outcomes, with treatment options limited to hydration or renal replacement therapies. The onset of AKI is often associated with a surfeit of reactive oxygen species. Here, it is shown that selenium‐doped carbon quantum dots (SeCQDs) have broad‐spectrum antioxidant properties and prominent renal accumulation in both healthy and AKI mice. Due to these properties, SeCQDs treat or prevent two clinically relevant cases of AKI induced in murine models by either rhabdomyolysis or cisplatin using only 1 or 50 µg per mouse, respectively. The attenuation of AKI in both models is confirmed by blood serum measurements, kidney tissue staining, and relevant biomarkers. The therapeutic efficacy of SeCQDs exceeds amifostine, a drug approved by the Food and Drug Administration that also acts by scavenging free radicals. The findings indicate that SeCQDs show great potential as a treatment option for AKI and possibly other ROS‐related diseases.