A Covalent Organic Framework Modified With Adenosine Triphosphate For Inhibiting Aβ Protein Aggregation

The toxicity of β-amyloid protein(Aβ)accumulation is considered to be one of the important causes of neurodegenerative diseases,especially Alzheimer’s disease(AD).One of the mainstream treatments for AD is to select inhibitors to delay or interfere with Aβ protein aggregation.Among them,nanoparticles(NPs)can effectively inhibit the aggregation of Aβprotein and prevent its fibrosis.Previous research results show that it is necessary to control the particle size and surface function of NPs as the focus of research.Spherical covalent organic framework nanoparticles(COFNPs)have significant application advantages,especially in the biomedical field.However,at the present stage,the COFNPs has many shortcomings,such as poor water dispersion,difficult to control the particle size,and difficult to realize the surface function.Therefore,it is very important to develop a method that can simultaneously control the particle size and functionalize the surface of COFNPs.Previous studies have shown that the mesoporous structure of COF can enhance the adsorption of Aβ protein through host-guest recognition,and the negatively charged phosphate group can specifically capture a variety of positively charged amino acids on Aβ protein.Inspired by this,on the basis of trying to optimize the preparation conditions of COF with buffer solution,this paper puts forward a method of using ATP(adenosine triphosphate)to assist in the synthesis of COFNPs,which plays the role of acid catalyst,nucleation inhibitor and surface function.Taking advantage of the hydrophilicity of phosphate groups on ATP,the water dispersion of COFNPs can be improved,and the particle size control,surface functionalization of COFNPs and host-guest interaction between COF and Aβ protein can be realized by onestep method.The characterization of the structural composition,morphology,crystallinity and particle size of COFNPs shows that the particle size of COFNPs synthesized by this method is in the range of 90200 nm,the surface is modified with ATP functional groups,and the crystallinity is good.In addition,this paper preliminarily studied the effect of COFNPs particle size on the inhibition of Aβ protein aggregation,and on this basis,we studied the difference of protein aggregation inhibition of COF synthesized by ATP and acetic acid on the surface of sphere COF.In addition,this paper preliminarily studied the effect of COFNPs particle size on the inhibition of Aβ protein aggregation,and on this basis,we studied the difference of protein aggregation inhibition of COF synthesized by ATP and acetic acid on the surface of sphere COF.The results showed that COFNPs with smaller particle size had a stronger inhibitory effect on the aggregation of Aβ protein,and COFNPs could delay the nucleation process.COFNPs with surface-modified ATP had a better effect on Aβ protein aggregation inhibition than COF catalyzed by acetic acid synthesis.In general,through the effective preparation of COF nanoparticles,a new method was explored to provide new materials for the design of Aβ protein aggregation inhibitors.