Black Phosphorus Nanosheets Protect Neurons by Degrading Aggregative α‐syn and Clearing ROS in Parkinson's Disease

Abstract Although evidence indicates that the abnormal accumulation of α‐synuclein (α‐syn) in dopamine neurons of the substantia nigra is the main pathological feature of Parkinson's disease (PD), no compounds that have both α‐syn antiaggregation and α‐syn degradation functions have been successful in treating the disease in the clinic. Here, it is shown that black phosphorus nanosheets (BPNSs) interact directly with α‐syn fibrils to trigger their disaggregation for PD treatment. Moreover, BPNSs have a specific affinity for α‐syn through van der Waals forces. And BPNSs are found to activate autophagy to maintain α‐syn homeostasis, improve mitochondrial dysfunction, reduce reactive oxygen species levels, and rescue neuronal death and synaptic loss in PC12 cells. It is also observed that BPNSs penetrate the blood–brain barrier and protect against dopamine neuron loss, alleviating behavioral disorders in 1‐methyl‐4‐phenyl‐1,2,3,6‐tetrahydropyridine (MPTP) induced mouse model and hA53T α‐syn transgenic mice. Together, the study reveals that BPNSs have the potential as a novel integrated nanomedicine for clinical diagnosis and treatment of neurological diseases.