光热型纳米金-共聚物超声造影剂的制备及其在体外和大鼠乳腺癌模型显像的实验研究

A photothermal ultrasound contrast agent:preparation,in vitro and in vivo investigation of gold nanoshelled poly(lactide-co-glycolic acid)nanoparticles

目的制备外包纳米金壳内载全氟丙烷(C_3F_8)的聚乳酸羟基乙酸(PLGA)光热型超声造影剂,观察其在体内外的超声显像效果及体外的光热效能。方法通过改进的乳化溶剂挥发法制备PLGA纳米粒子,包载C_3F_8气体后,再用种子生长法在PLGA表面形成纳米金壳,制备C_3F_8@PLGA@Au纳米粒子;检测其一般特性,采用近红外激光评估其体外光热效能;超声成像仪观察体外及大鼠乳腺癌模型成像效果。结果成功制备C_3F_8@PLGA@Au纳米粒子,该粒子的平均直径为(268.2±80.5)nm,多分散指数为0.196,Zeta电位为(-22.5±5.2)m V,无明显细胞毒性;在808 nm激光辐照下,粒子有很好的溶液光热效果;体外及大鼠乳腺癌模型超声成像实验中均有增强显像。结论成功制备了光热型纳米超声造影剂,其有良好的体外光热性能和体内外超声显像效果,可为乳腺癌诊治提供新思路。

Objective To prepare a photothermal ultrasound contrast agent with C3Fs filled-gold nanoshelled poly （laetide-co-glycolic acid） nanoparticles（ C3F8@PLGA@Au NPs ） and to investigate its photothermal effect and contrast enhanced ultrasound imaging capability. Methods The nanoscale agent was fabricated with modified emulsion-solvent evaporation method through filling C3Fs into PLGA,followed by the formation of gold nanoshell on the surface. The physicoehemical properties of C3F8@PLGA@Au NPs were characterized by electronic microscopy and dynamic laser scattering. And its photothermal effect was assessed via monitoring temperature increase under the laser irradiation in vitro. The ultrasonic diagnostic instrument was used to evaluate the ultrasound contrast behavior of C3F8@PLGA@Au NPs. Results The C3F8@PLGA@Au NPs were observed with spherical morphology, good dispersion（0.196 ）, and uniform size with average diameter of （268.2±80.5）nm and electric potential of （-22.5±5.2）mV. The NIT assay indicated the good biocompatibility of our NPs. The NPs showed good photothermal effect under laser irradiation （808 nm）. And the imaging results in vitro and in vivo demonstrated that C3F8@PLGA@Au NPs provided excellent contrast enhancement for ultrasound imaging. Conclusion The photothermal ultrasound contrast agent has been designed and fabricated. The preliminary studies demonstrate that C3F8@PLGA@Au NPs have excellent photothermal effect in vitro and ultrasound imaging capability in vitro and in vivo, which provides new thought for diagnosis and treatment of breast cancer.