The differentiation of neural stem cells via nanomaterials has attracted attention and has become a potential tool. However, the chirality effect in neural stem cell differentiation has not been investigated. Here, this study shows that chiral nanoparticles (NPs) with strong chirality can efficiently accelerate the differentiation of mouse neural stem cells (NSCs) into neurons under near‐infrared (NIR) light illumination. L‐type NPs are 1.95 times greater than D‐type NPs in promoting NSCs differentiation due to their 1.47‐fold endocytosis efficiency. Whole gene expression map analysis reveals that circularly polarized light illumination and chiral NPs irradiation significantly upregulate Map2, Yap1, and Taz genes, resulting in mechanical force, cytoskeleton protein action, and accelerated NSCs differentiation. In vivo experiments show that successful differentiation can further alleviate symptoms in Alzheimer's disease mice. Moreover, the clearance of L‐type NPs on amyloid and hyperphosphorylated p‐tau protein reachs 68.24% and 66.43%, respectively, under the synergy of NIR irradiation. The findings suggest that strong chiral nanomaterials may have advantages in guiding cell development and can be used in biomedicine.

Parkinson's disease (PD) is a common neurodegeneration disease. Unfortunately, there are no effective measures to prevent or inhibit this disease. In this study, biodegradable Mn 3 O 4 nanoparticles (NPs) in different shapes are prepared and enclosed them by {100}, {200} and {103} facets that exhibit facet-dependent protection against neurotoxicity induced by oxidative damage in a cell model of PD. Notably, Mn 3 O 4 nanorods enclosed by {103} facets exhibit high levels of enzyme-like activity to eliminate reactive oxygen specie in vitro. It is also determined that the uptake pathway of Mn 3 O 4 NPs into MN9D cells is mediated by caveolin. The data demonstrate that Mn 3 O 4 nanorods can be taken up by cells effectively and confer excellent levels of neuroprotection while the biodegradation of Mn 3 O 4 NPs in vivo is confirmed by photoacoustic image of Mn 3 O 4 NPs in brain at 60 d. Furthermore, the oxygen scavenging effect created by Mn 3 O 4 nanorods is successfully applied to a mouse model of PD; the amount of 𝜶-synuclein in the cerebrospinal fluid of PD mice is reduced by 61.2% in two weeks, thus demonstrating the potential application of facet-directed Mn 3 O 4 NPs for the clinical therapy of neurodegenerative disease.

Protein aggregation causes alpha-synuclein (α-syn) to change from its original physiological role to a pathological state, which is a potential pathogenic mechanism in Parkinson's disease. Chiral L/D-Cu x Co y S supraparticles (L/D-SPs) with CD value of 35 mdeg at 805 nm were fabricated using a simple wet-chemical method.The L/D-SPs prevented the α-syn monomers forming fibrils and triggered the α-syn fibrils to turn into monomers under 808 nm near-infrared (NIR) light illumination. In living MN9D cells, D-SPs reduced cellular damage, neuronal functional deficits and neuron loss caused by α-syn fibrils after NIR treatment within 10 min to prevent α-syn aggregation. Significantly, the reactive oxygen species (ROS) produced by D-SPs were 1.42 times higher than those produced by L-SPs. In vivo experiments showed that D-SPs had a protective effect on neuron damage caused by α-syn aggregate deposition, reduced the symptoms in a mouse model of Parkinson's disease and restored cognitive ability. After NIR light treatment, the amount of α-syn in a mouse model of Parkinson's disease decreased by more than 67.5%. At the same time, D-SPs could gradually decompose into small nanoparticles within 60 days, which could be excreted through the blood-brain barrier (BBB). This discovery paves the way for the treatment of neurodegenerative diseases using chiral SPs under NIR light irradiation.