Synthesis And Application Of Dual-modal Probes For Time-gated Luminescence/magnetic Resonance Imaging

Molecular imaging is a non-invasive bioimaging technique for characterizing biological processes at the cellular and molecular level,it has been attracted much attention in recent years because of its potential for accurate detection of of diseases in the early stages and monitoring of treatment effects.However,as each imaging modality has its intrinsic benefits and drawbacks,single-modality imaging is lacking in providing information on all aspects of structure and function.To break through the limitations of a single imaging modality,multimodal imaging,which integrates different imaging modalities to address unmet needs,has been used to solve the above problem.In this paper,we designed and synthesized two bimodal time-resolved luminescence（TGL）/magnetic resonance imaging（MRI）probes based on lathanide complexes.These probes exhibit high spatial resolution and high tissue penetration（for MRI）,and high sensitivity and high selectivity（for TGL imaging）,and could be powerful tools for molecular imaging technology.In this work,the luminescent PTTA-Tb³⁺complex,magnetic resonance contrast agent Gd³⁺-DO3A-NH₂ and a tumor-targeting molecule（folic acid,FA）were covalently bonded to the SiO₂ nanoparticles,and a bimodal TGL/MR imaging nanoprobe FA-Gd-Tb@SiO₂ was designed and synthesized for specific tumor binding and imaging.The as-prepared nanoprobe emits a strong green time-resolved luminescence,exhibits high r₁ relaxivities(r₁=22.3s^-1mM^-1);meanwhile,the modified folic acid（FA）on the surface of the nanoprobe makes it capable of targeting cancer cells.The above characteristics enable the nanoprobe to detect the cancer cells in vitro by TGL imaging and visualize tumor in vivo by MRI.Based on the previous work,a multifunctionalβ-diketone ligand,BHHBSB that can specifically react with HClO,was designed and synthesized.Its Eu³⁺complex,BHHBSB-Eu³⁺exhibits a strong red time-resolved luminescence.After reacting with HClO,BHHBSB was are oxidized and cracked,resulting in a decomposition and luminescence quenching of BHHBSB-Eu³⁺.After reacting with the increased concentrations of HClO,the luminescence intensities of BHHBSB-Eu³⁺gradually reduced until a complete disappearance.The dose-dependent luminescence decrease shows a good linearity between the luminescence intensity and the HClO concentration.（Limit of detection is 14.9 nM）.Furthermore,the Gd³⁺complex,BHHBSB-Gd³⁺,show a"turn-off"magnetic resonance response to HClO,its longitudinal relaxation rate（R1=1/T₁）gradually decreases with the increase of HClO concentration.The as-prepared dual-mode probe exhibits high selectivity and sensitivity,as well as high reaction rate.It can image HClO at various resolutions ranging from subcellular level to the whole body without a depth limit.Using this probe,TGL imaging of exogenous and endogenous HClO in living cells,and ex vivo luminescent imaging of endogenous HClO in LPS-induced acute liver and kidney injury of mice were successfully demonstrated.