| The magnetic resonance imaging (MRI) has been of wide interest onboth fundamental research and clinical diagnosis over recent years,because it is noninvasive, delivers no radiation burden, and offersreal-time3D images. The use of paramagnetic or super paramagneticmaterials as the MRI contrast agents could effectively enhance theresolution ratio and contrast ratio in MRI. Many new types of MRIcontrast agents with particular characteristics such as long cycle time,high targeting property and responsiveness, could be obtained withreasonable choice and modify of the magnetic materials, which willexpand a much more broad medical prospects for the MRI. Thepolyxometalates (POMs) is a kind of inorganic nanoclusters, which havebeen applied in the industrial production depanding on the specialcharacteristics of catalysis, redox and optics. In recent years, themulti-metal oxygen cluster has drawed extensive attention on account oftheunique properties in medical field. The primary experimental contentand conclusions are as follows:We design and synthesis three sandwich type Gd POMs, whichcombine similar frame structure but different heteroatom with P, Si, and B,respectively. Based on these molecules, we particularly evaluted theeffect of the change of heteroatom spcies on the water-solubility and pHstability of the POMs. Furthermore, the feasibility of these three POMs asMRI contrast agents was also discussed on the basis of the relaxationefficiency and cytotoxicity. The results showed that all the three POMs took better water-solubility than the existing commercial Gd complexes,which could stably dissolved in neutral and weak acid solution.Compared with that of the Gd-DTPA, these POMs present higherlongitudinal relaxtion efficiency. The volume difference of POMs,resulted from the diverse heteratom coordination, is responsible for thedifference of the rotational correlation time, finally led to a sequence ofthe longitudinal relaxtion efficiency is POM-1≈POM-2>POM-3, which isin accordance with the clinical1.5T MRI test. In addition, strongelectrostatic interactions were observed between the POMs and protein. Agradual increase in the electrostatic interaction strength was discoveredwith the increase of the charge number in POMs themselves, which isPOM-1<POM-2<POM-3. In comparison with in the water, the increscentlongitudinal relaxtion times of the POMs in protein solution areprolonged due to the slow rotation rate in protein solution caused by theabove mentioned electrostatic interaction. The increase amplitude presenta POM-1<POM-2<POM-3order, which is agreed with thechargeaugment of the POMs. On the other hand, the molecule stabilitiesin physiological environment are reduced, which led to an enhancedbiological toxicity and a consequence in the cytotoxicity strength ofPOM-1>POM-2>POM-3.In the subsequent work, two kinds of paramagnetic POMs materialswith large size difference were studied. One of them is Keggin typePOMs (coded POM-4), the other is double coupling Keggin type POMs(coded POM-2). Through the comparison of the two tpyes POMs, thebulk effect of the POMs on the solubility, stability, relaxivity efficiencyand the cytotoxicity are discussed. Acoording to our research, theelectrostatic interaction both happened in the protein solution with thetwo kinds of POMs, resulting a quenching of the characteristic fluorescence signal of human serum albumin solution along with theintroduction of the two POMs. As we discussed in the previous part, theelectrostatic interaction slows down the rotation of POMs in solution andbrings an improvement of the longitudinal relaxtion time. A slightlyamplification in the longitudinal relaxtion time was achieved because ofthe stronger electrostatic interaction due to the more charge number ofPOM-2, which possess a higher toxicity than POM-4according to afurther cytotoxicity tests. Combining the above two test conclusions, wethought that the POM-4moleculer was suitable for clinical application inthe future due to its smalls cytotoxicity than POM-2. |
PDF Full Text Request