Modulating efficient differentiation of neural stem cells into neurons by using plasmonic nanoparticles and the NIR II irradiation to boost therapy of Parkinson’s disease

Progressive loss of dopaminergic neurons is the primary pathological feature of Parkinson's disease (PD), which causes severe cognitive and motor dysfunction. In this context, transplantation of neural stem cells (NSCs) is the most promising approach to supply new dopaminergic neurons for the treatment of PD, which faces the challenge of precisely controlling the differentiation direction of NSCs. Herein, we report the efficient differentiation of NSCs into neurons boosted by the joint use of Cu2-xSe nanoparticles (CS NPs) with the second near-infrared (NIR-II) laser irradiation. We reveal the mechanism of neuronal differentiation of NSCs and find that the voltage-gated calcium channels (VGCC) of NSCs can be opened under the stimulation of CS NPs and NIR-II laser irradiation to trigger Ca2+/CaMK/CREB/c-Fos signaling pathway, which promotes the neural differentiation and survival. More importantly, when a mixture of CS NPs and NSCs was injected into the damaged striatum of 6-hydroxydopamine(6-OHDA)-induced PD mice and then irradiated with an external 1064 nm NIR-II laser, the NSCs were efficiently differentiated into dopaminergic neurons to effectively repair the damaged neural circuits in the nigra-striatum and ameliorate the motor disorders and anxiety of PD mice. These findings demonstrate the feasibility and importance of precise modulation of directional differentiation of NSCs into matured functional neurons in vivo and in vitro through advanced functional nanoparticles and nanotechnology, which offers a promising approach for the treatment of PD and other neurodegenerative diseases. [Display omitted] •Cu2-xSe nanoparticles (CS NPs) and NIR Ⅱ laser irradiation promote neural stem cells (NSCs) differentiation into neurons.•The voltage-gated calcium channels (VGCC) of NSCs can be opened to trigger Ca2+/CaMK/CREB/c-Fos signaling pathway.•The transplanted NSCs assited with CS NPs and 1064 nm NIR-Ⅱ laser ameliorate the symptoms of PD mice.