Preparation And Biocompatibility Of Metal-organic Frameworks FeBTC Loaded With Artemisinin And Its Derivatives

Metal-Organic Frameworks(MOFs)are porous materials formed by combining metal ions as connection points and organic ligands as support.With high specific surface area,flexible structure,and easy modification performance,in recent years,MOFs show excellent performance in many sites like catalysis,gas adsorption,biomedical research,etc.Iron-based MOFs nanoparticles have been reported as drug carriers due to their relatively good biocompatibility without heavy metal ions.However,the preparation of iron-based MOFs on the material surface by layer-by-layer growth method(also known as liquid phase epitaxial growth method)for drug delivery has not been reported.In this paper,FeBTC and FeBTC loaded with artemisinin,and its derivatives were prepared using the layer-by-layer growth method at room temperature.The materials and biological functions of FeBTC and FeBTC loaded with artemisinin,and its derivatives were evaluated.The preparation process of polydopamine coating containing more phenolic hydroxyl groups was screened out by quantitative analysis.On the surface rich in phenolic hydroxyl groups,the surface-grow iron-based MOFs were prepared by layer-by-layer self-assembly method.Then the iron-based MOFs were characterized by XRD,XPS,SEM,water contact angle test.The results showed that the iron-based MOFs have typical FeBTC structure and characteristics,and the surface is rough and super-hydrophilic.FeBTC loaded with different proportions of artemisinin was prepared on the surface of Ti by adding artemisinin with molar ratios of 3:1,3:2,and 3:3 in the 1,3,5-benzene tricarboxylic acid solution.SEM characterization results showed that the addition of artemisinin had a significant influence on the nucleation and growth of FeBTC on the surface of the material,which changed the uniform distribution of point growth into the dispersed cluster growth.The release of Fe³⁺in the solution after soaking for a different time was detected by atomic absorption spectrometry.The results showed that the addition of artemisinin increased the release of Fe³⁺per unit area,indicating that it accelerated the degradation of FeBTC.The release test results of artemisinin showed that the samples in each group have prominent burst release within one day and then sustained slow release.The results of in vitro culture of endothelial cells and smooth muscle cells showed that both FeBTC and artemisinin-loaded FeBTC surfaces were not conducive to cell adhesion and growth,which might be due to their super-hydrophilic surface.Artemisinin-loaded FeBTC could significantly reduce the inflammatory factor TNF-?which is secreted by macrophages,while the expression of anti-inflammatory factor IL-10 had no significant difference compared with the control group.FeBTC loaded with dihydroartemisinin and artesunate were prepared on Ti surface by a similar preparation method as artemisinin-loaded FeBTC mentioned above.After co-incubation with macrophages,FeBTC containing dihydroartemisinin and artesunate significantly inhibited the secretion of TNF-?and promoted the expression of IL-10.Endothelial cells were cultured in vitro by simulating the inflammatory environment.The results showed that FeBTC loaded with artemisinin and its derivatives inhibited the adhesion and growth of endothelial cells to a certain extent by inhibiting the production of inflammatory factor TNF-?.In conclusion,FeBTC loaded with artemisinin and artemisinin derivatives showed a certain function of inhibiting macrophage inflammation.The sample loaded with artesunate could significantly promote the expression of anti-inflammatory factor IL-10,delivering the optimal anti-inflammatory function.