Chiral Nanoparticles Force Neural Stem Cell Differentiation to Alleviate Alzheimer's Disease

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.