The Preliminary Study Of Mn-doped ZnS Quantum Dots On Its Synthesis,Properties And Radiosensitization Mechanism

Objective：To synthesize the water-soluble Mn-doped ZnS quantum dots (QDs) andinvestigate its fluorescence imaging,MRI relaxation enhancement,radiosensitizing effectsand the possible mechanisms.Methods： Water-soluble ZnS:Mn quantum dots were prepared by co-precipitationmethod and its materials characterization was detected by Dynamic light scattering (DLS)analyses and X-ray diffraction (XRD); fluorescence spectrophotometer and invertedfluorescence microscope were used to investigate fluorescence imaging and MRIrelaxation enhancement was investigated by nuclear magnetic resonance analyzer andMagnetic resonance imaging system. In the radiosensitizing study， The killing effects ofZnS:Mn QDs on Hela and U373cells growth was detected by MTT assay; clonogenicassay was used to measure the radiosensitization and survival curve was drawed. In orderto study radiosensitization mechanisms,reactive oxygen species assay kit was used todetect the reactive oxygen species (ROS) in U373cells,Flow-cytometry was used tomeasure cell cycle distribution and western blotting was used to measure the expression ofCaspase-3and Bcl-2of U373cells．Results：1.The synthetized quantum dots was of water-soluble, averaged sizes of5nm andstable structure.2.ZnS:Mn QDs’ strong orange florescent lights and small particle diameters made itown the property of entering the cell and imaging.3.ZnS:Mn QDs could shorten T1relaxation time(r1=8.05，r2=21.93).4.The outcome of MTT assay suggested that ZnS:Mn QDs may produce aconcentration-dependent inhibition of Hela and U373cells growth. 5. ZnS:Mn QDs showed radiosensitization effects to a certain extent in U373cells(SERD0＝1.16).The survival curve and related parameters indicated that the value ofD0,SF2,N and Dq of Group Q+R was lower than those of Group R.6. The expression level of ROS in U373cells of Group Q+R was significantly higherthan of Group R(Group R and Group Q+R:43.0±0.8,60.9±1.4, respectively; P＜0.05)7. The distribution of cell cycle varied in Group R and Group Q+R, Group Q+Rshowed more G2/M phase arrest than Group R (Group R and Group Q+R:41.99±1.23%,34.03±1.58%, respectively; P＜0.05).8.The expression of Bcl-2and Caspase-3proteins in U373cells was proved bywestern blotting: campared with Group R，the express level of Bcl-2protein wasdownregulated with Group Q+R. By contrast, the express level of Caspase-3protein ofGroup Q+R was upregulated.Conclusions：1. Water-soluble ZnS:Mn QDs was synthetized correctly.2.ZnS:Mn QDs owned the property of intracellular fluorescence imaging, it was also apotential T1MRI Contrast Agents.3.ZnS:Mn QDs could enhance radiation sensitivity of U373cells in vitro．4.The possible sensitizing mechanism may be by the following pathways: raisingexpression level of ROS, strengthening radiation-induced G2/M phase arrest,decreasingthe expression level of Bcl-2protein and increasing the expression level of Caspase-3protein.