Preparation Of Iron-based MRI Contrast Agents And Its Application In Breast Cancers Theranostic

Malignant tumor has become one of the major diseases threatening human life and health.In recent decades,people have invested a lot of manpower,material resources and money to try to solve this problem.However,there are many problems need to overcome in the process.Early detection,diagnosis and treatment have become the key in cancer theranostics.Although the existing diagnostic methods,such as X-ray,computed tomography(CT),positron emission tomography-computed tomography(PET-CT)can achieve the diagnosis of cancer in a certain extent,they bring some side effects to patients from the radiation.Magnetic resonance imaging(MRI)technology solves this problem well.The development of MR contrast agents has also greatly improved the imaging effect of MRI.Among them,iron-based MRI contrast agents are more and more favored by scientific researchers for their good T₂ imaging effect,excellent biocompatibility,hard to decompose and low dosage.Based on the iron-based MRI contrast agents,further design and optimization of this kind of contrast agent and its applications in the diagnosis and treatment of breast cancer are presented in this thesis.First,a new trojan targeting strategy is designed.Superparamagnetic iron oxide nanoparticles(SPION)were embedded by albumin spheres(AN),then folate acid(FA)and pH-sensitive polymer were grafted on the surface of SPION.The design not only ensures the long circulation of SPION in vivo,but also avoids the uptake of nanoparticles by normal tissues or cells.The pH response experiment of the polymer showed that the polymer on the surface of AN could be hydrolyzed rapidly at pH 5.5and existed stably at pH 7.4.MR studies show that the composite nanoparticles have better r₂ and r₂/r₁ values than commercial contrast agent Resovist^?.In vitro and in vivo imaging showed that the composite nanoparticles can greatly shorten T₂ relaxation time and can be used as an effective T₂-weighted MRI contrast agent.Second,a smart glutathione(GSH)and hydrogen peroxide(H₂O₂)dual responsive signal inversion MRI contrast agent(SPION@DMSN@PEG)is designed.MRI relaxation data shows that the designed contrast agent have higher r₂ and r₂/r₁ values,which are significantly higher than those of commercial contrast agents of Resovist^?and Feridex^?,can be an excellent potential application value.The imaging data in vitro showed that the contrast agent showed a certain T₁ weighted effect at a relatively low iron concentration,with the increase of iron concentration,it transformed into T₂weighted imaging.The contrast agent provides T₂-weighted imaging in the tumor site,and effectively switches to T₁-weighted imaging as DMSN is degraded by the action of GSH and H₂O₂that abound in the tumor microenvironment.The preparation of the contrast agent solves the artifacts caused by bleeding,calcification and metal deposition in a certain extent.At the same time,it takes into account the unparalleled spatiotemporal resolution and sensitivity o f multimodal imaging,avoids the confusion of the using dosages of drugs.Third,based on the previous research,SPION and DOX were embedded simultaneously into AN and wanted to achieve the visualization of tumor treatment.The results show that the load capacity of SPION and DOX is 7.02%and 4.93%,respectively.MTT characterization proved that nanoparticles have a certain therapeutic effect on tumor.The results of in vivo experiments in mice showed that the composite nanoparticles had high biosafety.For the treatment in vivo,necrosis was appeared in the tumor site when treated with drugs,while tumor rapid growth appeared in the site untreated with drugs.In summary,this work successfully prepared the visual theranostic nanoparticles,greatly reducing the question of use of multi-and large doses drugs,reducing the pain and risk of patients due to the multiple drug administration.In summary,this paper reports the design and improvement of tumor targeting of the materials to develop the highly sensitive and multimodal MRI contrast agents.The strategy presented in this paper combines imaging and treatment to realize the visual treatment of lesion.