| Objective:Ultrasound imaging is one of the most widely used imaging in clinic,which can detect the difference of acoustic impedance between normal tissue and pathological tissue to achieve pathological parts imaging.It has the advantages of low cost,speediness and convenience,and can realize intravascular and extravascular imaging;Chemical exchange saturation transfer(CEST)imaging technology can be used for the early diagnosis of brain diseases(such as brain tumor,stroke,etc.).It has the advantages of high sensitivity,high resolution and no radiation,and has potential application value in clinical diagnosis.In order to enhance the image effect,it is necessary to add some contrast agents.However,single-mode imaging sometimes cannot meet clinical needs.Whereupon,in this paper,PEG-PLLA was used to encapsulate both salicylic acid and perfluoropentane to prepare US/CEST MR dual-mode contrast agent,which realized the complementary advantages of the two imaging methods.Methods:L-lactide was recrystallized first,and then ring-opening polymerization of PEG with l-lactide was performed at 120?with octanoyl as catalyst to synthesize block copolymer PEG-PLLA.The structure and property of copolymer was analyzed by infrared spectrophotometry,H~1-NMR,X-ray diffraction and thermogravimetric analysis.Subsequently,the block copolymer was used to encapsulate salicylic acid and PFP to prepare nanoparticles by emulsion solvent evaporation method.The particle size and zeta potential were measured by laser particle size analyzer,and the stability was also investigated.In order to study the biocompatibility of PEG-PLLA,CCK-8 assay,scratch assay and hemolysis assay were carried out respectively.Finally,CEST MR and ultrasound imaging were studied in vitro and in vivo with dual-mode contrast agent on 7.0 T animal magnetic resonance scanner and 10 MHz ultrasonic imager respectively.Results:IR and H~1-NMR analysis demonstrated that PEG-PLLA was successfully prepared.XRD analysis showed that the crystal diffraction peaks of the block copolymer were weaker than that of PEG and PLLA from 40°to 80°,and thermogravimetric analysis showed that PEG-PLLA possessed a certain thermal stability.The particle size of salicylic acid nanoparticles was 223.8±2.5 nm nm,PDI was 0.153±0.020 and zeta potential was-39.6±1.9 m V.The stability assay showed that when nanoparticles were stored at 4?for one month,the stability was better.In the experimental concentration range,CCK-8 and scratch test proved that PEG-PLLA was less toxic to C6 cells,and hemolysis test showed that the copolymer had little hemolysis effect on red blood cells.CEST MR imaging experiments showed that the dual mode contrast agent could significantly increase the contrast of CEST MR imaging.When p H was 6.4 and the intensity of saturation radio frequency pulse was4.0?T,the imaging contrast was maximum,and the effect lasted for about 2 hours in the rat glioma experiment.US imaging assays demonstated that the phase transition effect and imaging contrast were the highest at 37?.What's more,it could also improve the imaging contrast of subcutaneous tumor on the nude mouse.Conclusion:This study demonstrated that the salicylic acid/PFP nanoparticles encapsulated by PEG-PLLA could improve the CEST and US imaging.In one word,there exists great clinical application potential for dual mode contrast agents. |
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