基于超支化聚醚的纳米级超声造影剂

Nano-Scale Ultrasound Contrast Agent Based on Hyperbranched Polyether

通过阳离子开环聚合合成了以超支化聚3-乙基-3-羟甲基环氧丁烷(HBPO)为疏水核、聚乙二醇(PEO)为亲水性链段的两亲性超支化聚醚(HSP),将HSP作为壳材料制得一系列超声造影剂(UCA),即HSP-UCA。采用动态光散射仪(DLS)、透射电子显微镜(TEM)、气相色谱-质谱联用仪(GC-MS)、超声成像仪等对HSP-UCA的粒径及体内外超声成像效果等进行了表征和分析。结果显示:随着PEO臂长的增加,HSP-UCA稳定性增加,导致其浓度增加;当PEO臂长增加到10时,HSP10-UCA的浓度最高,其平均粒径为517.3 nm,悬液的六氟化硫(SF6)体积分数为9.12×103,体外超声半衰期为3~5 min,同时在兔心脏内的显影效果很好。HSP10-UCA是一种纳米级超声造影剂,具有很好的体内外超声显影效果。

Hyperbranched polyether HBPO-star-PEO(HSP,HBPO:hyperbranched poly(3-ethl-3-oxetanemthanol;PEO:polyethyleneglycol))with different PEO arm lengths were synthesized by cationic ring-opening polymerization.A series of ultrasound contrast agents(UCA)were prepared using HSP as shell materials and SF6 as inner gas,which were named as HSP-UCA.The size,micromorphology,SF6 concentration and in vitro/in vivo ultrasound imaging effect of HSP-UCA were characterized by dynamic light scattering(DLS),transmission electron microscopy(TEM),gas chromatography-mass spectrometry(GC-MS),and ultrasound imaging instrument.The results showed that analogous to the effect of PEO arm length on the stability of the vesicles,the stability of UCA increased with the PEO arm length,resulting in an increase in its concentration.When the PEO arm length was increased to 10,high concentration of HSP10-UCA was obtained with an average size of 517.3 nm,the SF6 volume fraction of 9.12×10−3 and the in vitro ultrasound half-life of 3−5 min.in vivo Ultrasound test of HSP10-UCA in rabbit heart showed good ultrasound contrast effect.Before the injection of nano-scale HSP10-UCA,the ultrasound echo signal inside the heart was very low and the internal structure could not be observed by ultrasound imaging.However after intravenous injection of HSP10-UCA,the rabbit heart was quickly perfused,its internal structure was slowly appeared.The average ultrasound contrast duration of HSP10-UCA was 50−60 s.The above results indicate that the nano-scale HSP10-UCA is an excellent ultrasound contrast agent and its good ultrasound contrast effect will be beneficial to its future applications in the ultrasound imaging of tumor tissues.