Boosting neurite outgrowth and anti-oxidative stress for treatment of Parkinson's disease by biomimetic ultrasmall nanoparticles

Parkinson's disease (PD) is characterized with the loss and death of dopaminergic neurons in the substantia nigra (SN) and striatum, and its initial pathological feature is neuritic degeneration. Herein, we report the outgrowth of neurites and the treatment of PD boosted by cell-membrane coated biomimetic Cu2_xSe-SC79 nanoparticles (denoted as CSS@CM NPs). We reveal that CSS NPs promoted neurite outgrowth via p-Akt/p-CREB signaling pathway and enhanced the anti-apoptotic effects by upregulating Bcl2/Bax ratio. The biomimetic CSS@CM NPs can target neurons through the specific interactions between the neuronal membrane surface vascular cells adhering to molecule-1, and alpha 4 beta 1 integrin expressed by RAW 264.7 cells. More importantly, the athletic ability of PD mice treated by biomimetic CSS@CM NPs was significantly improved due to the improvements in synaptic function and the decrease of the apoptosis level of neurons. The levels of glial fibrillary acidic protein, ionized calcium binding adapter protein 1, and enzyme tyrosine hydroxylase of treated PD mice were nearly restored to those of healthy mice. Our study demonstrates that synergistically reducing synaptic damage and protecting neuron apoptosis shows great potential in treatment of PD and other neurodegenerative diseases.