Research On The Responsive Fe₃O₄-ZIF-8 Nuclear Magnetic Resonance Contrast Agent

Magnetic resonance imaging（MRI）has become one of the most powerful medical diagnostic tools because it can provide anatomical images with high spatial resolution in a non-invasive and real-time way.However,because of the low sensitivity of MRI,contrast agents are widely used clinically for enhancing the contrast between tumors and normal tissues.Recently,stimuli-responsive contrast agents have been extensively studied because they can exhibit different relaxation signals in the lesion and normal tissues upon triggered by the abnormal microenvironment（e.g.acidic pH,overexpressed GSH,etc）at the lesion sites,providing higher sensitivity and signal-to-noise ratio.Iron oxide nanoparticles（Fe₃O₄）with good biocompatibility are promising MRI contrast agents.Fe₃O₄ has excellent T₁ imaging performance in small size form,and good T₂ imaging performance in large size form or aggregates.To date,several Fe₃O₄ based T₁-T₂ switching contrast agents have been reported,but that refer to T₂-T₁ switching contrast agents are still limited.We herein reported a Fe₃O₄-based T₂-T₁ switching contrast agent for effective tumor imaging in vivo by utilizing a pH and GSH-responsive ZIF-8 as matrix.This paper is divided into the following three chapters:In the first chapter,we introduce the principle of MRI,the types of contrast agents and the latest research progress.Then we elaborate the research significance and main research contents of our subject.In the second chapter,we mainly introduce the preparation methods and biological applications of the assembly of small size Fe₃O₄ nanoparticles（about 6nm）into Fe₃O₄-ZIF-8.Fe₃O₄ nanoparticles were prepared by high-temperature pyrolysis method and then ligand exchange to obtained water-soluble nanoparticles,which were further self-assemble into Fe₃O₄-ZIF-8 assembly using zeolitic imidazole frameworks（ZIF-8）as matrix.A series of solution experiments were carried out to verify that Fe₃O₄-ZIF-8 is able to disassemble and release the Fe₃O₄nanoparticles in a slightly acidic and low concentration GSH environment,leading to T₂/T₁ contrast transformation.In vivo T₁-weighted images of mice showed that Fe₃O₄-ZIF-8 displayed darkening contrast enhancement for liver,while darkening to brightening contrast enhancement at tumor site,giving large inverse contrast for distinguishing the normal and tumor tissues.In the third chapter,we summarize the experimental data.