Mitochondria-targeted nanozymes eliminate oxidative damage in retinal neovascularization disease
2022
Xue, Bai | Ge, Mengyue | Fan, Kelong | Huang, Xinglu | Yan, Xiyun | Jiang, Wei | Jiang, Bing | Yang, Zhenglin
Retinal neovascularization is typically accompanied by hypoxia-induced oxidative injury in the vascular system. This study developed an ultrasmall (6–8 nm) platinum (Pt) nanozyme loaded mitochondria-targeted liposome (Pt@MitoLipo) to alleviate hypoxia and eliminate excess reactive oxygen species (ROS) for effective retinal neovascularization disease therapy. Pt nanozymes possess superoxide dismutase (SOD) and catalase (CAT) cascade enzyme-like activities, which convert cytotoxic O₂•⁻ and H₂O₂ into nontoxic H₂O and O₂. Triphenylphosphonium (TPP)-conjugated liposomes were coated on the surface of Pt nanozymes to increase their biocompatibility and help them penetrate the cell membrane, escape from the lysosomal barrier, and target mitochondria, thus achieving precise scavenging of mitochondrial O₂•⁻ and relief from hypoxia. Using an oxygen-induced retinopathy (OIR) mouse model, we demonstrated that Pt@MitoLipo nanozymes significantly suppressed hypoxia-induced abnormal neovascularization and facilitated avascular normalization of the retina in vivo without any noticeable toxicity. This study provides a promising way to break through cellular barriers and target scavenging mitochondrial O₂•⁻ and illustrates the potential of ROS-scavenging and hypoxia relief in retinal neovascularization disease therapy.
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