Minocycline nanoplatform penetrates the BBB and enables the targeted treatment of Parkinson's disease with cognitive impairment.

Parkinson's disease (PD)-induced motor dysfunction and cognitive impairment are becoming increasingly common due to global population aging. However, efficient treatment strategies for these conditions are still lacking. Recent studies indicated that neuroinflammation and neuronal apoptosis could greatly worsen the symptoms of PD. Therefore, anti-apoptotic and anti-inflammatory drugs could be useful in the management of PD. In the present study, minocycline (MIN)-loaded Fe3O4 nanoparticles (Fe3O4-MIN NPs) were prepared for the targeted treatment of PD. Owing to their near-infrared (NIR) irradiation-induced photothermal effects, the Fe3O4-MIN NPs could cross the blood-brain barrier (BBB), thus enhancing the delivery of Fe3O4-MIN NPs to the brain parenchyma. Subsequently, the Fe3O4-MIN NPs exerted strong anti-inflammatory effects and alleviated neuroinflammation in the brain. Furthermore, they exerted anti-oxidative effects, scavenging excessive reactive oxygen species in the brain parenchyma and thus protecting both dopaminergic and hippocampal neurons from neuroinflammation and apoptosis. Consequently, Fe3O4-MIN NPs + NIR treatment attenuated the motor dysfunction and cognitive impairment observed in PD mice. Notably, the Fe3O4-MIN NPs also showed high biocompatibility. Hence, these BBB-penetrating MIN-loaded Fe3O4 NPs demonstrate great therapeutic potential for PD accompanied by cognitive impairment.