载硫化铋叶酸靶向相变型超声/光声双模态对比剂体外寻靶及显像研究

In Vitro Targeting and Imaging of Floate-targeted Phase-transition Ultrasound/photoacoustic Dual-modal Contrast Agent Carrying Bismuth Sulfide

目的研制载硫化铋(Bi2S3)叶酸受体靶向相变型纳米粒(FPBS-PFH-NPs),观察其体外细胞寻靶、相变及超声/光声成像效果。材料与方法用双乳化法制备叶酸靶向载 Bi2S3及相变材料全氟已烷(PFH)的纳米粒 FPBS-PFH-NPs,检测其基本理化性质;观察 FPBS-PFH-NPs 对宫颈癌 Hela 细胞和正常人肝 L02 细胞主动靶向能力。用加热板、高强度聚焦超声(HIFU)及光声仪作用于纳米粒,观察其相变情况及体外超声/光声成像。结果 FPBS-PFH-NPs 的粒径约(439.7±93.7)nm,电位约(-15.5±5.8)mV,紫外吸收峰与单纯 Bi2S3 相对应。靶向组大量 FPBS-PFH-NPs 紧密结合在 Hela 细胞周围;而载 Bi2S3 非靶向相变型纳米粒(NPBS-PFH-NPs)与 Hela 细胞未见明显结合,FPBS-PFH-NPs 和 NPBS-PFH-NPs 均未与 L02 细胞有明显结合。加热板、HIFU 及光声仪作用 FPBS-PFH-NPs 后,发生液气相变,显著增强超声显影。光声仪激发 FPBS-PFH-NPs 后,光声信号较前明显增强。结论成功制备出 FPBS-PFH-NPs,对 Hela 细胞具有良好的靶向性及体外增强超声/光声双模态显像。

Purpose To develop folate receptor-targeted phase-shift nanoparticles (FPBS-PFH-NPs) carrying bismuth sulfide (Bi2S3) and observe the cell targeting, phase transition, and ultrasound/photoacoustic imaging effect in vitro. Materials and Methods The double emulsion method was used to prepare folate-targeted nanoparticles FPBS-PFH-NPs carrying Bi2S3 and phase-transition perfluorohexane (PFH) to detect their basic physicochemical properties. The active targeting ability of FPBS-PFH-NPs against cervical cancer Hela cells and normal human liver L02 cells was observed. The heating plate, high-intensity focused ultrasound (HIFU) and photoacoustic instrument were used to act on nanoparticles to observe their phase-transition and in vitro ultrasound/photoacoustic imaging. Results The particles size of FPBS-PFH-NPs was about (439.7±93.7) nm, the electric potential was about (-15.5±5.8) mV, and the ultraviolet absorption peak corresponded to the pure Bi2S3. In the targeted group, a large number of FPBS-PFH-NPs were bonded to Hela cells;non-targeted phase-transition nanoparticles (NPBS-PFH-NPs) carrying bismuth sulfide were not found to have bonded to Hela cells, and both FPBS-PFH-NPs and NPBS-PFH-NPs did not bond to L02 cells obviously. After the heating plate, HIFU and photoacoustic instrument acted on FPBS-PFH-NPs, liquid-gas phase transition occurred and ultrasound imaging was enhanced significantly. After FPBS-PFH-NPs were excited by the photoacoustic instrument, photoacoustic signal intensity was enhanced more significantly than before. Conclusion The FPBS-PFH-NPs are prepared successfully, which has better targeting to Hela cells and enhanced ultrasound/photoacoustic dual-modal imaging in vitro.