Phosphorylation of covalent organic framework nanospheres for inhibition of amyloid-β peptide fibrillation

• DOI: 10.1039/d2sc00253a
• Publication Date: 2022-04-22T00:01:17Z
• Authors: Linli Yao; Zhe Zhou; Suxiao Wang; Qichao Zou; Hang-Xing Wang; Li-Xin Ma; Shengfu Wang; Xiuhua Zhang
• Keywords: Isothermal Titration Calorimetry; Surface Modification; Nanomaterials; Fibrillation; Amyloid (mycology)

The development and exploration of new nanostructural inhibitors against Alzheimer's disease (AD)-associated amyloid-β (Aβ) fibrillation have attracted extensive attention become a frontier in nanomedicine. However, focusing on finding an effective nanostructure is one the most challenging parts therapeutics task. Herein, nanoscale spherical covalent organic frameworks (COFs) via post-synthetic functionalization with sodium phosphate (SP) groups channel networks were found to efficiently inhibit Aβ fibrillation. as-prepared uniform SP-COF nanospheres high surface area, good crystallinity, chemical stability characterized by multifarious microscopic spectroscopic techniques. Moreover, molecular dynamics simulation together kinetics cytotoxicity assay experiments shows that there restricted-access adsorption channels SP-COFs which formed cavities size functional accommodated peptide sequence significantly affected Aβ. Transmission electron microscopy (TEM), dynamic light scattering (DLS) monitoring, isothermal titration calorimetry (ITC), Fourier transform infrared (FT-IR) circular dichroism (CD) spectra measurements, confocal imaging observation performed understand inhibition mechanism influencing factors SP-COFs. To our knowledge, strategy first COF-based anti-amyloidogenic nanomaterials affinity specific targeting, are crucial for AD prevention treatment.