Chiral Skeletons of Mesoporous Silica Nanospheres to Mitigate Alzheimer’s β-Amyloid Aggregation

Chiral mesoporous silica (mSiO₂) nanomaterials have gained significant attention during the past two decades. Most of them show a topologically characteristic helix; however, little attention has been paid to the molecular-scale chirality of mSiO₂ frameworks. Herein, we report a chiral amide-gel-directed synthesis strategy for the fabrication of chiral mSiO₂ nanospheres with molecular-scale-like chirality in the silicate skeletons. The functionalization of micelles with the chiral amide gels via electrostatic interactions realizes the growth of molecular configuration chiral silica sols. Subsequent modular self-assembly results in the formation of dendritic large mesoporous silica nanospheres with molecular chirality of the silica frameworks. As a result, the resultant chiral mSiO₂ nanospheres show abundant large mesopores (∼10.1 nm), high pore volumes (∼1.8 cm³·g^–1), high surface areas (∼525 m²·g^–1), and evident CD activity. The successful transfer of the chirality from the chiral amide gels to composited micelles and further to asymmetric silica polymeric frameworks based on modular self-assembly leads to the presence of molecular chirality in the final products. The chiral mSiO₂ frameworks display a good chiral stability after a high-temperature calcination (even up to 1000 °C). The chiral mSiO₂ can impart a notable decline in β-amyloid protein (Aβ42) aggregation formation up to 79%, leading to significant mitigation of Aβ42-induced cytotoxicity on the human neuroblastoma line SH-ST5Y cells in vitro. This finding opens a new avenue to construct the molecular chirality configuration in nanomaterials for optical and biomedical applications.