产气脂质纳米粒的制备及其光声成像研究

A study of a novel gas-generating liposomal nanoparticle for photoacoustic imaging

目的研制一种可生物降解,其产物可完全排除机体的光声成像材料。方法采用薄膜水化法加脂质体挤出法制备产气脂质纳米粒;应用肉眼、光镜、电镜、激光粒径仪检测纳米粒物理特性;光声成像仪、红外光谱仪探讨纳米粒光声成像机制;应用光声成像仪检测纳米粒体外、体内成像效果及安全性。结果肉眼观察碳酸氢铵脂质纳米粒呈透明乳状,粒径(230.9±54.58)nm,电位(-22.8±5.75)m V,稳定性较好。纳米粒光声信号随浓度、温度、时间增加而增强;体外激光辐照对细胞无损伤作用。经鼠尾静脉注入纳米粒,各组正常裸鼠血氨浓度均较对照组升高(均P<0.05),但精神体征与对照组无明显改变。荷瘤裸鼠肿瘤局部出现光声信号,于4 h达到高峰,随后逐渐消失;激光能量对皮肤及皮下组织均无损伤作用。结论碳酸氢铵脂质纳米粒可用于光声成像,且安全、有效、价廉、无副作用。

Objective To develop a biodegradable contrast agent for photoacoustic imaging.Its biodegradation products could be fully removed from a living organism.Methods The gas-generating liposomal nanoparticles were prepared by thin-film hydration and liposome extrusion methods.The general physical characteristics were detected by light microscope,electron microscope and laser particle size analyzer.The photoacoustic imaging mechanism was explored by photoacoustic imaging device and infrared spectrometer.The photoacoustic imaging quality and safety were evaluated by photoacoustic imaging device in vitro and in vivo.Results The nanoparticles were spherical with regular morphology and uniform size distribution,there was no obvious aggregation.The mean particle size of nanoparticles was（230.9±54.58）nm with uniform distribution and dispersion,Zeta potential was（-22.8 ±5.75）m V.The intensity and the area of the photoacoustic signals were enhanced corresponding to the increase of concentration,temperature and time.There was no damage to cells by laser radiation.During in vivo test,serum ammonia concentrations for various treatment groups were higher than those in the control group（all P0.05）,but vital signs observation of nude mice showed that there had no significant changes in foraging and movement compared with the control group.Photoacoustic signals were detected from the tumor,reached the peak in 4 h and then disappeared gradually.There was no damage to the skin and subcutaneous tissue by laser radiation.Conclusion The gas-generating nanoparticles of liposome encapsulating ammonium bicarbonate solution can be used for photoacoustic imaging,and it is safe,effective,cheap and free of side effects.