Gene therapy has shown great potential for neurodegenerative diseases with complex pathology. However, its therapeutic effect is limited due to the delivery barriers and its own single function. Herein, self-catalytic small interfering RNA (siRNA) nanocarriers (S/Ce-PABMS) are developed to catalyze delivery process and treatment process for synergistic treatment of neurodegenerative diseases. On the one hand, the rough surface of the S/Ce-PABMS mediated by ceria (CeO2 ) nanozymes can catalyze cellular uptake in the delivery process, so that S/Ce-PABMS with acetylcholine analogs penetrate the blood-brain barrier and enter neurons more effectively. On the other hand, the CeO2 nanozymes can catalyze the treatment process by scavenging excess reactive oxygen species, and cooperate with siRNA-targeting SNCA to decrease the α-synuclein (α-syn) aggregation and alleviate the Parkinsonian pathology. Moreover, the S/Ce-PABMS treatment reduces the number of activated microglia and regulates the release of inflammatory cytokine, thereby relieving neuroinflammation. After treatment with S/Ce-PABMS, dyskinesia in Parkinson's disease model mice is significantly alleviated. The finding shows that the self-catalytic nanocarriers, S/Ce-PABMS, have great potential in the treatment of neurodegenerative diseases.
Keywords: brain delivery; nanozymes; neurodegenerative diseases; self-catalysis; siRNA; synergistic treatment.
© 2021 Wiley-VCH GmbH.