Interaction Between Medicinal Molecules With Biological Macromolecules And Application Of Nanocomposstes Fe₃O₄/rGO

At present,the study of the interaction between drug molecules and biological macromolecules provides important information for understanding and grasping the operation and metabolism of drugs in vivo,revealing clinical pharmacokinetics,guiding rational drug use,and exploring pharmacological effects from the molecular level.At the same time,it HSA important guiding significance for the design and development of new drugs with high efficiency and low toxicity.In this paper,the effects of several drug molecules and nanocomposites as drug carriers on the conformation and toxicity of biomacromolecules were studied at the molecular level.The main contents of this paper are as follows:Chapter 1:In the first section,explains the reasons,background and significance of several medicinal molecules and biological macromolecules as research objects;the significance of studying the interaction between micromolecule and biological macromolecules;an overview of nanocomposites and the research background as drug carriers.Chapter 2:In the second section,under the condition of simulating human physiology,the effects of vitamin C（Vit.C）on the combination of aspirin（ASP）and human serum albumin（HSA）were studied by fluorescence,three-dimensional fluorescence（EEM）,fourier transform infrared spectroscopy（FT-IR）,circular dichroism（CD）and cyclic voltammetry（CV）.In this system,the interaction of Vit.C and HSA,ASP and HSA two binary system,Vit.C on the interaction of ASP and HSA and ASP on the interaction of Vit.C and HSA two ternary system were studied.The experimental results show that,in the binary system,the quenching method between Vit.C and HSA was dynamic quenching,the main binding force was hydrophobic force;the quenching mode between ASP and HSA was static quenching,the main binding force was hydrogen bond and van der Waals force;in the ternary system,based on the CV,FT-IR,EEM and CD experiments,it was confirmed that the existence of ASP will affect the binding of HSA and Vit.C.At the same time,the binding constant of（HSA-ASP）-Vit.C was lower than that of the binary system HSA-Vit.C by fluorescence experiment;the binding constant of（HSA-Vit.C）-ASP was basically unchanged compared with that of the binary system HSA-ASP.Namely taking Vit.C first in daily life will not affect the absorption of ASP in human body,which was beneficial to human health.On the contrary,people who have just taken ASP should not take Vit.C immediately,because the existence of ASP will reduce the absorption of Vit.C to the human body.Chapter 3:In the third section,We synthesized Fe₃O₄/rGO nanocomposites as drug carriers to study the interaction of HSA with free curcumin（Cur）and/or Cur-Fe₃O₄/rGO complexes in vitro.Fluorescence quenching experiments showed that the binding constant of Cur with HSA increased significantly in the presence of Fe₃O₄/rGO.In addition,the loading and interaction mechanism of Cur on Fe₃O₄/rGO nanocomposites were studied by resonance light scattering（RLS）,atomic force microscopy（AFM）,circular dichroism（CD）and fourier transform infrared（FT-IR）.The results show that drug loading was a complex process,which was not controlled by simple adsorption,but the formation of complex,and the low toxicity of Fe₃O₄/rGO to HSA.In the presence of Fe₃O₄/rGO,the binding constant of Cur and HSA increases significantly,which enhances the interaction between Cur and HSA.Chapter 4:Based on the previous system study,we found that the magnetic nanocomposite Fe₃O₄/rGO a good drug loading effect,however resveratrol（RES）as a chemopreventive agent for tumor treatment of atherosclerosis,disease of heart head blood-vessel chemoprophylaxis agent,HSA poor water solubility and low bioavailability.Therefore,in this paper,we studied the positive role of Fe₃O₄/rGO as a drug carrier in the interaction between RES and ct-DNA.The fluorescence experiment was used to calculate by the Stern-Volmer equation,the quenching constant of ct-DNA-RES system decreases with the increase of temperature.So,the quenching mode of ct-DNA-RES system was static quenching,while the quenching mode of ct-DNA-RES system was still static quenching in the presence of Fe₃O₄/rGO,but the binding constant of ct-DNA-RES increases from 4.40±0.26×10⁴L mol^-1 to 9.33±0.04×10⁴L mol^-1.It was found that Fe₃O₄/rGO formed a ternary complex with RES and ct-DNA by ultraviolet spectrum（UV-vis）and resonance light scattering experiments（RLS）and scanning electron microscope（SEM）.At the same time,fourier transform infrared spectroscopy（FT-IR）and circular dichroism（CD）experiments show that Fe₃O₄/rGO nanomaterials have low toxicity.These results confirm that Fe₃O₄/rGO nanocomposites have good application potential,can be used as a good drug carrier in a wide range of therapeutic methods.