载黑色素脂质纳泡的制备及体外多模态显像实验研究

Preparation of melanin-based lipid nanobubbles for enhancing multimodal imaging in vitro

目的制备一种包载黑色素的多模态脂质纳泡(MNBs)造影剂,观察其体外超声、光声、MR显影效果。方法采用三氯甲烷注入—冷冻干燥—全氟丙烷充气法制备MNBs和普通脂质纳泡(NBs),检测MNBs的一般特性(形态、粒径、黑色素装载量、稳定性),对不同浓度MNBs进行体外超声、光声、MR成像并进行定量对比分析。结果 MNBs形态规则,粒径分布均匀,透射电镜显示MNBs成功包裹黑色素颗粒。黑色素的载药量为90.53μg/mg。体外显影实验示随MNBs和NBs浓度的增加,超声造影效果明显增强,MNBs和NBs的超声造影表现无明显差异,相对信号强度差异无统计学意义(P>0.05);随MNBs浓度的增加,光声和MRI显影效果增强,NBs无光声和MRI显影效果。结论成功制备出一种包载黑色素的多模态脂质纳泡造影剂,可明显增强超声、光声、MR显影效果。

Objective To prepare multi-modality melanin-based lipid nanobubbles （MNBs） contrast agents, and to inves- tigate their manifestations of ultrasound （US）, photoacoustic （PA） and MRI in vitro. Methods MNBs and lipid nanobub- bles （NBs） were prepared with the method of CHCl3-injection, freeze-drying and C3F8 inflation. The characteristics （shape, grain diameter, loading capacity of melanin and stability） of MNBs were obseved. US, PA and MRI were detected in vitro and the images were quantitatively analyzed. Results MNBs presented with homogenized size distribution, and transmission electron microscope （TEM） images demonstrated that the melanin particles were successfully entrapped into nanobubbles. Meanwhile, the loading capacity of melanin was 90.53 μg/mg. US signal increased in vitro with the rise of MNBs and NBs concentration. The ultrasonic manifestations of MNBs and NBs were the same, and the relative signal en- hancement had no significant difference （P〉0.05）. With the increased concentration of MNBs, the PA and MRI signals were stronger, but NBs showed no evident enhancement. Conclusion Multi-modality MNBs contrast agents are prepared successfully, which can enhance US, PA and MR imaging.