Mitochondrial‐Targeting Mesoporous Polydopamine Nanoparticles for Reducing Kidney Injury Caused by Depleted Uranium

Abstract Depleted uranium (DU), when accidentally released from the nuclear industry, can enter the human body and cause kidney damage, as DU induces oxidative damage and apoptosis through mitochondrial pathways and inflammatory reactions. The existing nanoparticles used to treat DU injury have low bioavailability and poor targeting. In this study, mesoporous polydopamine (MPDA), poly‐(ethylene glycol) (PEG), and triphenylphosphonium (TPP) are combined to develop a novel mitochondrion‐targeting bifunctional nanoparticle, MPDA–PEG–TPP, and confirm that it can protect the kidneys from DU. This study demonstrates the high selectivity of MPDA–PEG–TPP for uranyl in uranyl chelate assays and its promising efficiency in uranyl sequestration from the kidneys, lungs, and femurs, following immediate or delayed administration of MPDA–PEG–TPP nanoparticles. In vitro assays confirm its efficiency in removing reactive oxygen species and targeting the mitochondria. In addition, in vitro and in vivo assays confirm that MPDA–PEG–TPP can reduce mitochondrial dysfunction and ameliorate kidney injury. These results suggest that MPDA–PEG–TPP is a valuable agent for ameliorating the DU‐induced kidney injury.