Preliminary Biosafety Evaluation of Surface PVP Modified Magnetic Nanoparticles
Objective To study the biological safety of superparamagnetic Fe3O4 nanoparticles(Fe3O4 NPs@PVP),and to provide a basis for the clinical application of magnetic nanoparticles.Methods Fe3O4NPs@PVP was added to the culture medium containing rat fibroblast cells at final concentrations of 0.25,0.5,0.75 and 1 mg/ml,and cell via-bility was measured by the Alarma blue assay;Fe3O4NPs@PVP with a diameter of 130 nm was prepared in equal volumes at concentrations of 2,5,10 and 25 mg/kg as suspensions for later use,thirty rats were randomly divided into control group,low-dose group,medium-dose group,high-dose group and extremely high-dose group,with 6 rats in each,the control group received an intravenous injection of 0.2 ml saline into the tail vein,while the other dose groups received an intravenous injection of 0.2 ml of Fe3 O4NPs@PVP suspension at concentrations of 2,5,10 and 25 mg/kg respectively,and the rats were observed continuously for 14 days after the injections.At the end of the experimental period,blood samples from the abdominal aorta were taken from the rats by enzyme-linked immunosorbent assay(ELISA)to assess immune globulin IgG levels and to measure the contents of alanine aminotransferase(ALT),aspartate aminotransferase(AST),total bilirubin(TBIL),albumin(ALB),blood urea nitrogen(BUN),creatinine(Cr),creatine kinase(CK)and lactate dehydrogenase(LDH).Pathological examinations were conducted on the heart,liver,spleen,lung and kidney of the rats.Results When Fe3O4NPs@PVP was applied to rat fibroblasts at different final concentrations,the cell survival rate decreased directly with the increase of the concentration;when the final concentration of Fe3O4 NPs@PVP was 1 mg/ml,the viability value of rat fibroblasts was still 81％.Compared with the control group,the levels of AST in rats in the high-dose group and the levels of AST,BUN and LDH in rats in the extremely high-dose group significantly increased,the differences between the two groups were statistical-ly significant(all P＜0.05);compared with the extremely high-dose group,the level of ALT in rats in the high-dose group and the level of LDH in rats in the medium-dose group were lower,the differences between the two groups were statistically signifi-cant(all P＜0.05).Compared with contral group,the level of IgG in rats in midium-dose group was lower(P＜0.05).Patho-logical results showed that the heart,liver,spleen,lung and kidney of rats in the control group maintained good integrity without obvious lesions.Myocardial cells in other groups showed no hypertrophy,necrosis or fibrosis;the structure of hepatic lobules was normal,and there was no narrowing or blockage of hepatic blood vessels;some rats in the medium-dose group showed red pulp hyperplasia in their spleen slices,while splenic cells in low-dose group,medium-dose group,high-dose group and extremely high-dose group showed no necrosis,inflammation and fibrosis,and the structure of splenic nodules was normal;there was no abnormal inflammation or fibrosis in the alveolar walls of the lungs,and the structure of the alveoli was normal,no diffuse edema was observed in the interstitium of the lungs;the glomeruli showed no fibrosis,and the structure of renal tubules was normal.Conclusion After intravenous injection of Fe3O4NPs@PVP into rats,the rats survives normally within 14 days,with no signifi-cant pathological changes observe in any organs;even at extremely high-doses,Fe3O4NPs@PVP does not produce fatal toxicity to the rats.These results indicates that Fe3O4NPs@PVP has good biosafety and lays a foundation for subsequent clinical experi-mental research.
Magnetic nanoparticlesVivo toxicityBiosecurityPolyvinylpyrrolidone
NETL
NSTL
万方数据
