Catalytic‐Enhanced Lactoferrin‐Functionalized Au‐Bi2Se3 Nanodots for Parkinson's Disease Therapy via Reactive Oxygen Attenuation and Mitochondrial Protection

Overexpression of reactive oxygen species in the substantia nigra pars compacta destroys dopaminergic neurons and accelerates the pathological process of Parkinson's disease (PD). In this study, a new hydrophilic nano-bioconjugate, lactoferrin (Lf)-modified Au-Bi₂ Se₃ nanodot (ND) for efficient PD therapy is developed. In particular, the Lf-Au-Bi₂ Se₃ NDs exhibit strong blood-brain barrier (BBB) permeation. The Lf-Au-Bi₂ Se₃ NDs can also serve as multiple enzymes such as superoxide dismutase, catalase, glutathione peroxidase, and peroxide. These NDs are located close to the mitochondria and thus maintain the mitochondrial membrane potential as well as control the cellular ROS level. In vivo results further demonstrate that the NDs can improve the memory and mobility of PD mice; permeation of the BBB, protection of mitochondria, and suppression of dopaminergic neuron loss in the substantia nigra pars compacta are also observed. It is anticipated that these new Lf-Au-Bi₂ Se₃ NDs with excellent biocompatibility, multienzyme functionality, and BBB permeability will open new opportunities for PD therapy.