Synthesis Of Cerium-based Nanomaterials For Tumor Diagnostics Application

Cancer is a serious threat to human life,and early prevention,diagnosis and treatment of cancer are the main means to reduce morbidity and mortality.The traditional cancer diagnosis and treatment procedures are usually carried out by doctors with the help of medical imaging technology and radiotherapy technology after the patients present clinically obvious symptoms to hospitals,which are characterized by low sensitivity and poor targeting,and cannot achieve early diagnosis and treatment of cancer.Advances in the field of nanotechnology and biotechnology have promoted the development of nanomedicine,which brings new hope for early diagnosis and treatment of cancer.By using nanomaterials for cancer diagnosis and treatment,highly sensitive diagnostic reagents and sensors prepared by combining the unique physical and chemical properties of nanomaterials with optical,electrical and magnetic technologies can realize the labeling,imaging and targeting of tumor tissues and cells,which have great potential and practical application in early diagnosis and treatment of cancer.Cerium is the most abundant rare earth elements and can form two valence states,cerium（III）and cerium（IV）,through electron gain or loss.Cerium oxide has been applied in catalyst,polishing powder,electronic ceramic material,UV absorbing material,luminescent material,etc.In recent years,cerium oxide has been found to have the mimetic activity of various biological enzymes（such as superoxide dismutase,catalase,phosphatase,peroxidase and oxidase）,as well as the ability to scavenge hydroxyl radicals and nitrogen oxide radicals,and has been gradually applied in the biomedical field.As the research progresses,cerium oxide is also reported to have unique biomedical activities such as antibacterial,anti-inflammatory,anti-tumor and anti-radiation,which can be used in the treatment of various diseases,showing an attractive prospect for medical applications.Currently,research on the application of cerium nanomaterials（Ce NPs）in medical diagnosis and treatment is still in its infancy,and the exploration of various biomedical functions of Ce NPs is still a popular topic of research.Ce NPs have been used to treat a variety of diseases including hair loss,osteoporosis,enteritis,arthritis,diabetes,stroke,Alzheimer’s disease,etc.In addition,Ce NPs can also promote tissue regeneration and be used to construct drug and gene delivery vectors,which have broad application potential in the field of disease diagnosis and treatment.This thesis aims to synthetize novel cerium-based nanomaterials and have explored the related technologies for cancer diagnostic application.This thesis consists of six main chapters as follows:（1）Synthesis of cerium nanohollow spheres for drug carriers and CT imaging applicationsIn this section,we firstly synthesized cerium hollow structured nanospheres by a simple solvothermal method.The surface of cerium nanospheres were modified with chitosan and prepared a CS@Ce O2-X-Pp IX nanotherapeutic system by loading the phototherapeutic agent protoporphyrin IX（Pp IX）as a model drug.The CS@Ce O2-X-Pp IX was investigated for in vivo CT scan imaging and therapy on mouse tumor models.The results showed that the CS@Ce O2-X-Pp IX nano-therapeutic system can be used as a nano-drug carrier for targeted drug release to the acidic tumor microenvironment and CT scan imaging of the tumor site,which has great potential for in vivo and in vitro tumor treatment integration.（2）Synthesis of cerium-coated CT-FI dual-mode contrast agent for imaging applicationIn this section,a layer of Ce O2-X was coated on the outside of Cd Te@Si O₂ and modified with carboxymethyl chitosan（CMC）to construct the CMC-functionalized Cd Te@Si O₂@Ce O2-X for CT-FI bimodal contrast studies on mouse tumor models.The results showed that the CMC-functionalized Cd Te@Si O₂@Ce O2-X could be targeting deposited in the acidic tumor microenvironment.The CMC-functionalized Cd Te@Si O₂@Ce O2-X can be used for targeted CT-FI dual-modality imaging to the acidic tumor microenvironment（3）Synthesis of cerium-bridged MRI-FI dual-mode contrast agents for imaging applicationIn this section,the MRI probe Fe₃O₄ and the OI probe Cd Te QDs were interlinked by the adsorption of cerium（III）ions to form the Fe₃O₄-Ce-Cd Te magnetic fluorescent compounds.Then the Fe₃O₄-Ce-Cd Te compounds were modified with silicon oxide and could be used for MRI-FI dual-modality imaging on the tumor mouse model.（4）Synthesis of cerium-doped CQDs for fluorescence imaging and Fe³⁺detection applicationsIn this section,the folic acid modified cerium-doped carbon quantum dots（Ce-CQDs-FA）were synthesized in one step by simple hydrothermal method The Ce-CQDs-FA were used for targeted imaging of cancer cells and Fe³⁺detection studies.The results showed that the Ce-CQDs-FA could perform the targeted fluorescence imaging of cancer cells expressing folate receptors and detect Fe³⁺in blood samples with a linear range of 0-2 m M（R²=0.99）.