Synthesis And Bioimaging Applications Of Lanthanide Complex-Based Luminescence Probes For Hypochlorous Acid

Among various luminescence(fluorescence/phosphorescence)molecular probes,the probes using lanthanide complexes as luminophores have special properties of long luminescence lifetimes,large Stokes shifts and sharp emission profiles,which enable them to be suitably combined with time-gated(or time-resolved)luminescence detection technique,to eliminate the interference of autofluorescence during the imaging detection of complicated biological samples.On the other hand,owing to the unlimited penetration depth and high spatial resolution,Gd3+complex-based magnetic resonance imaging(MRI)is another hotspot in the researches of modern medicine imaging.In this doctoral dissertation several novel lanthanide complex-based luminescence probes for hypochlorous acid(HCIO)have been designed and synthesized,and their applicability for bioimaging was investigated.Based on the HClO-triggered luminescence quenching of ?-diketonate-Eu3+complexes,a silica-based ratiometric luminescence nanoprobe for HClO,RTLNP(ratiometric time-gated luminescence nanoprobe),was designed and synthesized by decorating the surface of the Tb3+complex-encapsulated silica nanoparticles with a tetradentate ?-diketone-Eu3+ complex.After the probe is reacted with HClO,its red luminescence from the Eu3+complex disappears,but green luminescence from the Tb3+ complex keeps unchanged,which enables the probe to be used for the ratiometric luminescence detection of HCIO under time-gated mode.RTLNP possessed the advantages of good selectivity,high sensitivity and rapid luminescence response,allowing it to be successfully used for the ratiometric luminescence imaging of HClO in live cells,zebrafish and Daphnia magna under time-gated mode.By incorporating triphenylphosphonium and morpholine moieties with a strongly luminescent tetradentate ?-diketone-Eu3+complex BHHBCB-Eu3+,two Eu3+complex-based luminescence probes that can respond to HClO in mitochondria and lysosomes,Mito-BHHBCB-Eu3+ and Lyso-BHHBCB-Eu3+,were designed and synthesized,respectively.The organelle-location features of the probes were demonstrated by the co-staining imaging experiments of the probes and the commercially available mitochondria-and lysosome-targeted fluorescence indicators with Pearson's correlation coefficients are 0.94 and 0.91,respectively.Using the two probes,the time-gated luminescence imaging of HClO in mitochondria and lysosomes of live cells was realized.By introducing the ligand DPBT into the structure of a bidentate ?-diketonate-Eu3+complex,a new luminescence probe for HClO,[Eu(L)3(DPBT)].was synthesized.This probe not only can emit red luminescence of Eu3+ complex at the excitation of visible light over 400 nm,but also has a good mitochondria-targeting feature,which allowed the probe to be successfully used for the luminescence imaging of HClO in live cells and mice.In addition,the smart bandage that can be used for the in situ real-time monitoring of HCIO in the skin wound of mice was prepared by immobilizing[Eu(L)3(DPBT)]into the hydrogel.Using the bandage,the real-time evaluation of wound infection status was realized.By covalently coupling the complex DOTA-Gd3+with BHHBCB-Eu3+,an amphiphilic Gd3+-Eu3+ heterometallic complex was synthesized.After self-assembly of the as-prepared complex,a luminescence-magnetic resonance bimodal responsive nanoprobe for HCIO,SADP,was constructed.On the basis of detailed characterization results of the probe for luminescence-magnetic resonance dual-modal detection of HCIO in aqueous and live cell samples,the probe was used for the detection of HClO in models of rheumatoid arthritis and drug-induced liver injury of mice.The results demonstrated the potential of the probe for the diagnosis of inflammation-relative diseases.