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

Abstract

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.

Chiral nanomaterial-based approaches for diagnosis and treatment of protein-aggregated neurodiseases: current status and future opportunities

“…The d -Asp COF NSs exhibited a higher binding affinity with Aβ 42 with respect to l -Asp COF NSs. 109 The role of stereochemistry was also assessed with triplex metallohelices enantiomers, i.e. Λ and Δ for the inhibition of Aβ peptides.…”

Downsizing Porphyrin Covalent Organic Framework Particles Using Protected Precursors for Electrocatalytic CO2 Reduction

“…Controlling the aggregation of COF crystallites represents one of the major challenges in the COF field, and several approaches have been developed over the past decade. [ 9 ] COF particles with sizes ranging from 10 nm to 1 µm based on boronate, imine, or ketoenamine linkages have been reported by using appropriate solvents, [ 10 ] low temperatures, [ 11 ] modulators, [ 12 ] surfactants, [ 13 ] or protecting groups. [ 13b ] However, it is worth mentioning that these strategies for suppressing aggregation usually have as a common prerequisite that all the COF precursors need to be dissolved to form a homogeneous solution.…”

Ambient Synthesis of Porphyrin-Based Fe-Covalent Organic Frameworks for Efficient Infected Skin Wound Healing

“…24,25 With the rapid advancement of covalent organic frameworks (COF), their application in the biological field have sparked considerable interest. 26,27 5,10,15,20-Tetrakis (4aminophenyl) porphyrin (TAPP), a structurally symmetrical photosensitizer equipped with free amino groups, can serve as a monomeic block for the construction of COF with phototherapeutic capabilities. 28−31 Furthermore, the incorporation of metal active sites into photosensitized COF, achieved through covalent bonds and metal ligands, offers new avenues for the creation of versatile multifunctional nanoplatforms.…”

“…Porphyrin-based photosensitizers are extensively employed in PDT and photothermal therapy (PTT) due to their ability to generate highly ROS and heat. , However, their limited water solubility and propensity to aggregate and precipitate in blood present challenges that restrict their efficiency and clinical utility. , To address these issues, researchers have recently developed nanomaterials based on photosensitizers. , With the rapid advancement of covalent organic frameworks (COF), their application in the biological field have sparked considerable interest. , 5,10,15,20-Tetrakis (4-aminophenyl) porphyrin (TAPP), a structurally symmetrical photosensitizer equipped with free amino groups, can serve as a monomeic block for the construction of COF with phototherapeutic capabilities. − Furthermore, the incorporation of metal active sites into photosensitized COF, achieved through covalent bonds and metal ligands, offers new avenues for the creation of versatile multifunctional nanoplatforms. , It is worth noting that achieving a uniform distribution of metal sites within metal-covalent organic frameworks (MCOFs) is imperative to prevent agglomeration and the deactivation of metal catalysts during catalytic reactions. − Moreover, the presence of mutually independent one-dimensional pore channels within crystalline MCOFs enhances mass transfer and promotes the interaction of reactants with catalytically active sites. Our envisioned application of porphyrin-based MCOFs involves the synergistic enhancement of antimicrobial and antibiofilm effects through the integration of PDT, PTT, and CDT triple modality cotherapy.…”