Aspartic Acid-Assisted Size-Controllable Synthesis of Nanoscale Spherical Covalent Organic Frameworks with Chiral Interfaces for Inhibiting Amyloid-β Fibrillation

Covalent organic framework nanospheres (COF NSs) have garnered special attention due to their uniform sphere morphology, adjustable particle size, and mesoporous microenvironment. However, methods to control an optimal particle size scale while achieving solution dispersibility and specific surface properties remain underdeveloped, which precludes many of the biomedical applications. Here, we propose and develop a general strategy to access simultaneous size control and surface functionalization of uniform spherical COF NSs in a single step using aspartic acid (d-/l-Asp) that plays center roles in an acid catalyst, hydrophilicity, size-controllable synthesis, and chiral enantiomer. In this study, for the first time, we have employed a surface chemistry engineering study to create a variety of nanoscale spherical COFs and subsequently measure parameters to evaluate the effectiveness of Asp in the regulation of the particle size. Moreover, the potential utilization of the d/l-enantiomeric Asp-COF NSs in preventing β-amyloid (Aβ) aggregation is investigated by analyzing their interactions with Aβ amyloids using a multitechnique experimental approach. To our knowledge, our strategy is the first synthesis of hydrophilic COF NSs with an optimal length scale and a chiral-selective targeting surface, which are crucial for the inhibition of Aβ fibrillation for Alzheimer's disease prevention.