Experimental Study Of Superparamagnetic Iron Oxide Nanoparticles For T₁WI Enhancement

Part Ⅰ Preparation and biosafety evaluation of ultrafine super paramagnetic iron oxideNanoparticlesObjective Preparation of ultrafine superparamagnetic iron oxide nanoparticles,characterization of their structure and physicochemical properties,evaluation of their biological safety and feasibility as MRI T1WI enhanced contrast agent.Method A healthy male New Zealand white rabbit was taken as the research object,and a certain concentration of Fe3O4@DDT-PMAA nanoparticles was injected to perform an MRI upper abdominal scan and measure the abdominal aorta T1 value.Then,different concentrations of Fe3O4@DDT-PMAA nanoparticles were injected,and then MRI scans were performed to screen the appropriate concentration of Fe3O4@DDT-PMAA nanoparticles for in vivo imaging.At the appropriate concentration,different doses of Fe3O4@DDT-PMAA nanoparticles were injected,and then the MRI scan was used to screen the optimal dose of Fe3O4@DDT-PMAA nanoparticles for in vivo imaging.VX2 tumor tissues were collected and rabbit VX2 liver cancer models were prepared.They were divided into 2 groups(3 in each group),Gd-DTPA was injected into the ear margin vein,and Fe3O4@DDT-PMAA nanoparticles were injected into the other group for enhanced scanning.Observe the in vivo imaging effects of Gd-DTPA and Fe3O4@DDT-PMAA nanoparticles.T1 weighted MR images of rabbit VX2 liver cancer model were scanned and injected with Fe3O4@DDT-PMAA nanoparticles at Omin,2min,12min,22min,32min,42min,52min at different time points,and the excretion of Fe3O4@DDT_PMAA was observed.Observe the injection concentration and dosage of Fe3O4@DDT-PMAA nanoparticles in vivo,imaging effect and excretion route.Fe3O4@DDT-PMAA nanoparticles were synthesized by the co-precipitation method,and their size,hydrated particle size,and magnetic stability were characterized.The results of Fe3O4@DDT-PMAA in vitro nuclear magnetic resonance imaging were observed and the T1 relaxation rate was calculated.Cytotoxicity test,in vivo toxicity test,and pharmacokinetic changes were used to evaluate the biological safety of Fe3O4@DDT-PMAAnanoparticles.Result1.The particle size distribution of Fe3O4@DDT-PMAA is uniform,the particle size is(6.3±1.3)nm,the hydrodynamic diameter is 37.5nm;the magnetic stability of Fe3O4@DDT-PMAA is good,and it still has good magnetic stability after dilution2.Fe3O4@DDT-PMAA relaxation rate r2/r1=1.25.Compared with distilled water,the signal strength of Fe3O4@DDT-PMAA increased significantly and with the increase of Fe concentration,the T1 signal strength tended to further increase.3.Fe3O4@DDT-PMAA nanoparticles have no obvious hemolysis and cytotoxicity;no significant tissue damage to brain,heart,liver,spleen,lung,kidney and other major organs.4.Fe3O4@DDT-PMAA nanoparticles are mainly distributed in the liver,spleen and kidney tissues,of which liver deposition is most obvious;Fe3O4@DDT-PMAA is excreted by the kidneys with urine after 30 hours.Conclusion Fe3O4@DDT-PMAA nanoparticles have higher stability,better imaging of tissue signals,better biocompatibility and safety,and have the potential to become T1WI agents.Part Ⅱ The study of superparamagnetic iron oxide nanoparticles on T1WI enhanced imaging of normal rabbit liver and VX2 tumorObjective To explore the feasibility and value of Fe3O4@DDT-PMAA nanoparticles for T1 WI enhanced imaging of normal liver and VX2 tumors in vivo.Method Taking healthy male New Zealand white rabbits as the study object,the T1 value of abdominal aorta was measured,and then different concentrations of Fe3O4@DDT-PMAAnanoparticles were injected respectively.Then,the appropriate concentration of Fe3O4@DDT-PMAAnanoparticles for in vivo imaging was screened by NMR scanning.At the appropriate concentration,different doses of Fe3O4@DDT-PMAA nanoparticles were injected respectively,and then the optimal dose for in vivo imaging of Fe3O4@DDT-PMAA nanoparticles was selected by NMR scanning.The best time of imaging was observed at the appropriate concentration and dose.VX2 tumor tissue was collected and VX2 liver cancer model was made in rabbits.The model was divided into two groups:one group was treated with GdDTPA,the other group was treated with F e3 O4@DDT-PM AA nanoparticles.The imaging effects of GDDTPA and F e3 O4@DDT-PM AA nanoparticles were observed.The liver images of Fe3O4@DDT-PMAA nanoparticles injected at different time points of 0min,2min,12min,22min,32min,42min and 52min were observed and the excretion of Fe3O4@DDT-PMAA was observed.The injection concentration,dose,imaging effect and excretion pathway of Fe3O4@DDT-PMAA nanoparticles were observed.Result1.With the increase of Fe3O4@DDT-PMAA nanoparticle concentration in vivo imaging effect,the signal intensity of MRI scan image increased obviously,and the signal intensity was positively correlated with Fe ion concentration.When the injection concentration reaches 800 μg/mL,the changes of each organ can be clearly observed.Although the concentration increased,the signal intensity further increased,but considering the cost and safety of the contrast agent,600 μg/mL was selected as the appropriate concentration for body magnetic imaging.2.At a concentration of 600 μg/mL,the T1 value is reduced to a minimum at 5.5mL/kg in 2min,and the dose of 4.0mL/kg is used to enhance the examination.Although the theoretical value of T1 is not the higerest,but because the Fe3O4@DDT-PMAA relaxation rate is lower,T1WI imaging does not affect the image quality at a high concentration dose,so the optimal imaging dose in vivo is 4.0mL//kg.3.At the appropriate concentration and optimal dose,the T1 value is the lowest within 2min,so the optimal time for in vivo imaging is 2min.4.The optimal concentration and dose of Gd-DTPA and Fe3O4@DDT-PMAA nanoparticles enhanced MR contrast T1WI imaging showed that The signal intensity of Fe3O4@DDT-PMAA nanoparticles is slightly higer than that of GD DTPA,and there is no difference in imaging effect.Gd-DTPA enhancement can be observed in the liver tumor area within 2 minutes after signal enhancement,and then weakened,while Fe3O4@DDT-PMAA nanoparticles imaging in liver tumor area is not effective.5.With the injection offe3O4@DDT-PMAA nanoparticles,the kidney T1WI showed an increasing trend,and then began to weaken.The same trend appeared in the imaging of the bladder.Conclusion The optimal injection concentration of Fe3O4@DDT-PMAA magnetic nanoparticles for in vivo imaging is 600 μg/mL,and the optimal injection dose is 4.0 mL/kg,the best time is within 2min.At this concentration and dose,the imaging effect of Fe3O4@DDT-PMAA T1 was slightly higer than that of GD DTPA,and there was no significant difference in imaging effect.Fe3O4@DDT-PMAA nanoparticles have poor imaging results in liver tumor areas.Fe3O4@DDT-PMAA is excreted through the kidney and bladder system,and has high safety.The imaging effect in the liver tumor area still needs further exploration and analysis.