Synthesis And Application Of Dual-modal Probes For Time-gated Luminescence And Magnetic Resonance Bioimaging

Bioimaging technology that enables visible of biological molecules is one of the important tool to the researches of medicine and life science,as well as clinical diagnosis.Considering any modality is not perfect enough to provide sufficient information on the structure and function of objective samples owing to their inherent limitation,Dual-or multi-modality molecular imaging techniques which can synergistically integrate their advantages,while reducing the disadvantages of each imaging technique to obtain more comprehensive information over any modality alone,are clearly attractive.In this dissertation,two lanthanide complex-based dual-modal magnetic resonance（MR）/time-gated luminescence（TGL）probes are designed and synthesized for imaging of glutathione（GSH）and tumor cells.These probes combine the high spatial resolution and deep tissue penetration of MRI with the sensitivity and selectivity of the TGL,and integrate the advantages of both techniques,which will provide a powerful tool for imaging of lesion tissue and bioactive molecules.Firstly,we constructed a dual-modal TGL/MRI nanoprobe,BB-Eu-BB@MnO₂,for glutathione（GSH）by anchoring luminescentβ-diketone-Eu³⁺complexes on layered MnO2nanosheets.The fabricated nanoprobe exhibited very week TGL and MR signals since the luminescence of the Eu³⁺complex was quenched by MnO₂ nanosheets and Mn atoms were isolated from water.Upon exposure to GSH,the MnO₂ nanosheets were rapidly and selectively reduced to Mn²⁺ions,resulting in remarkable enhancements of TGL and MR signals simultaneously.So the probe can be used as a dual-modal TGL/MRI nanoprobe for TGL and MRI of GSH.The as-prepared nanoprobe was successfully used for the TGL detection of GSH in human sera,TGL imaging of GSH in living cells and zebrafish,as well as dual-modal TGL/MR imaging of GSH in tumor-bearing mice.Based on previous research work,we developed a tumor-targetable dual-modal probe TF-Eu-Gd for TGL and MR imaging of tumor cells in vitro and in vivo.The multifunctional probe was constructed by incorporating a luminescent Eu³⁺complex,CDHH-Eu³⁺and a MR contrast agent,DO3A-Gd³⁺into a tumor-targeting protein,transferrin（Tf）.The as-prepared probe exhibits strong long-lived luminescence,pronounced longitudinal relaxivity and specifical binding to tumor cells.These features allowed it to be successfully used for the TGL imaging of tumor cells and tissues,as well as MR imaging of tumor in vivo.