Construction And Application Of Environmental Responsive Magnetic Resonance Contrast Agents

Magnetic resonance imaging?MRI?provides high application value to modern diagnostic medicine.Lung cancer poses a growing threat to the health of people in China.The use of contrast agents in MRI can improve the early diagnosis efficiency of tumor and help to depict the tumor and make plan for radiotherapy and chemotherapy.The traditional T₁ or T₂ single mode imaging has some limitations,and the development of new type of contrast agents?CAs?combining with stimulus response ability can provide more accurate and sensitive diagnosis for lesion.Based on the need to develop new types of MRI contrast agents to improve the contrast and sensitivity of MRI,three main projects were carried out in this dissertation:First,a kind of core-shell multilayer nanomaterial Mn-IOSP was synthesized for T₁-T₂ dual mode imaging and drug delivery for tumor.The T₁ contrast agent and DOX have been loaded into the shell for the pH responsive T₁ imaging and drug release,while the Fe₃O₄ in core could supply the T₂ contrast effect.The probe can be used as T₁-T₂ dual mode CAs in solution,cell and in vivo,and can target the tumor site through the link of c?RGDyK?in the surface and the EPR effect.Second,a ¹⁹F nuclear magnetic resonance spectroscopy?MRS?chemical shift probe has been developed.The probe responds to the overexpressed cathepsin B?Cat B?in lung cancer cells.A specific amide in the probe could be specially cut by Cat B and the structure of the probe changed,which eventually generated CF₃CH₂OH.The change of molecular structure caused the shift of ¹⁹F NMR signal.With this change,specific detection of Cat B can be achieved.The ¹⁹F NMR signals can be detected both before and after the response to Cat B,and the change of the chemical shift offers potentials to differentiate the focus from the healthy areas.Third,a new derivative of the cryptophane has been obtained for ultra-sensitive MRI detection for Cat B.The probe,combined with the detection of ¹²⁹Xe Hyper-CEST signal,provides a method for responsive detection for Cat B.There will be a structural change in the side chains of cryptophane after the cleavage of bond caused by Cat B,which give rise to changes in the chemical shift and signal intensity of ¹²⁹Xe in the cage of cryptophane.After reaction,there emerges a new ¹²⁹Xe Hyper-CEST signal with enhanced signal intensity.The probe has good biocompatibility,and can achieve sensitive detection for Cat B with low concentration of probe.In this paper,efforts for building new types of responsive-MR probes have been made,and three kinds of probe have been designed and synthesized to detect the biomarkers of lung cancer,and to some extent overcome the limitations of traditional T₁or T₂ single mode imaging.