Black Phosphorus Nanosheets as a Neuroprotective Nanomedicine for Neurodegenerative Disorder Therapy

Transition-metal dyshomeostasis is recognized as a critical pathogenic factor at the onset and progression of neurodegenerative disorder (ND). Excess transition-metal ions such as Cu²⁺ can catalyze the generation of cytotoxic reactive oxygen species and thereafter induce neuronal cell apoptosis. Exploring new chelating agents, which are not only capable of capturing excess redox-active metal, but can also cross the blood-brain barrier (BBB), are highly desired for ND therapy. Herein, it is demonstrated that 2D black phosphorus (BP) nanosheets can capture Cu²⁺ efficiently and selectively to protect neuronal cells from Cu²⁺ -induced neurotoxicity. Moreover, both in vitro and in vivo studies show that the BBB permeability of BP nanosheets is significantly improved under near-infrared laser irradiation due to their strong photothermal effect, which overcomes the drawback of conventional chelating agents. Furthermore, the excellent biocompatibility and stability guarantee the biosafety of BP in future clinical applications. Therefore, these features make BP nanosheets have the great potential to work as an efficient neuroprotective nanodrug for ND therapy.