Interaction Of Nano Fe₃O₄ And Nano ZnO With BSA And Combined Toxicity Of Nano Fe₃O₄ With CdCl₂

The rapid development of nanomaterials and nanotechno logy and their contributions to human society are obvious to all.With the increasing application of nanomaterials in the field of biomedicine,nanobiological effects have attracted more and more attention.When nanomaterials dispersing in the environment,they pose a threat to organisms exposed to them.Nanoparticles can enter the blood of living organisms by respiration,skin,oral administration,and intravenous injection.Nanoparticles are several orders of magnitude smaller than a cell and much smaller than red blood cells in the blood,and the nanoparticles in blood can move freely.There are more than 1,000 proteins in the blood,and nanoparticles must interact with the proteins in the blood.The interaction between nanoparticles and proteins not only change the biological behavior of nanoparticles in vivo,such as uptake,distribution and metabolism,but also affect the structure and function of the adsorbed proteins.Therefore,the study of the interaction between nanoparticles and proteins is conducive to the design of nanomaterials with good biocompatibility and provides a basis for the safe application of nanomaterials.The first chapter:It is a brief review of the nanoparticles-protein interaction process and its influencing factors of adsorption process.The results of the interaction between nanoparticles and proteins are introduced from two aspects of protein and nanoparticles.The influence of the interaction between nanomaterials and proteins on the application of nanomaterials in biomedicine is analyzed,and some research methods of nanoparticles-protein interactions are introduced.The second chapter:The interactions between BSA and nano Fe3O4,nano Zn0.4Fe2.6O4,nano SiO2 or nano ZnO were studied.The results showed that the tested nanoparticles had different adsorption capacities for BSA.The interaction of nano-Fe3O4 and BSA formed nanoparticle-protein corona.The formation of nanoparticle-protein corona caused the aggregation of nanoparticles,but did not affect on the internal structure of Fe3O4 nanoparticles.Further studies showed that the formation of nanoparticle-BSA corona not only changed the secondary structure of BSA,but also resulted in the hydrolysis of BSA,indicating that nano-Fe3O4 has the ability to hydrolyze BSA.Nano-Zn0.4Fe2.6O4 exhibited a lower ability to hydrolyze BSA compared to nano Fe3O4,indicating that the doping of Zn could inhibit the hydrolysis of BSA by nano-Fe3O4.Nano ZnO and nano SiO2 did not hydrolyze BSA.Free Fe2+and Fe3+also could not hydrolyze BSA.In addition,nano-Fe3O4 could not hydrolyze gamma globulin in blood.Nowadays,there is no literature about hydrolysis of protein by other nano particles.The discovery of the hydrolysis of protein by nanoparticles opens a new window for the study of the biological effects of nano Fe3O4.The third chapter:The hydrolysis of protein in the nanoparticles-protein corona by pepsin was studied.The results showed that the formations of protein corona on nano Zn0.4Fe2.6O4,nano Fe3O4,nano SiO2,nano ZnO and nano Ag inhibited the hydrolysis of BSA in these protein coronas by pepsin in different degrees.Interestingly,that ZnO nanoparticles could completely inhibit hydrolysis of BSA in protein corona by pepsin.The inhibition of nano ZnO was very strong in a wide pH range(pH 1.5-6.8)and a large particle size range(35-100 nm).The results show that nano-ZnO may be used as the carrier of protein drugs,because it can prevent the proteolysis of loaded proteins by proteases in vivo during the drug delivery process.Whether nano ZnO inhibits the hydrolysis of proteins in its protein corona by other proteases than the pepsin needs further study.In chapter 4,we evaluated combined toxicity of environment pollutants Fe3O4 nanoparticles(nano-Fe3O4)and cadmium chloride(CdCl2)in the small intestine of mice.The results showed that Fe3O4 nanoparticles(nano-Fe3O4)and CdCl2 have a negative synergistic toxicity in the small intestine of mice.Oral nano-Fe3O4 did not show obvious toxicity in the small intestine of mice.In contrast,oral CdCl2 caused significant oxidative stress in the small intestine of mice.CdCl2-induced oxidative stress resulted in inflammatory response in the small intestine as indicated by the significant increases in the levels of cyclooxygenase-2 and nitric oxide synthase as well as the inflammatory cell infiltration in the small intestinal tissue.Co-exposure to nano-Fe3O4 and CdCl2 significantly attenuated CdCl2-induced damage in the small intestine through reduction of oxidative stress and inflammatory response.Nano-Fe3O4 and CdCl2 had negative cooperative effects on the biodistributions of Fe and Cd in the small intestine due to mutually competitive inhibition of Fe and Cd uptake.The reduction of Cd accumulation in the tissue and the inhibition of Cd-induced deprivation of tissue Fe by nano-Fe3O4 played two key roles in the protective effect of nano-Fe3O4 on CdCl2-induced oxidative damage.Nano-Fe3O4 are suitable candidates as oral delivery of MRI contrast agents and drugs for patients with the Cd-induced diseases of the gastrointestinal tract organs.