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制备一种纳米级的载药超声造影剂,该纳米粒可有效累积分布至肿瘤深层部位,且体外实验证明,在升高温度或近红外光辐照下可实现纳米粒尺寸的纳米-微米转变:评价其体外粒径变化规律、体外超声显像效果及体内分布情况。所制备的纳米粒呈球形,脂质膜中可见中空金纳米球(hollow gold nanoparticle,HAu NS)的负载,粒径为302±5 nm,分散性指数为0.195±0.018,分布较均匀。在近红外光辐照(1或2 W·cm~(-2))下导致含有该纳米粒的溶液(以HAu NS计,0.2、0.04和0.02 g·L~(-1))升温迅速,利用激光粒度仪的控温功能,发现升温至52℃左右时即可检测到一定量的微米级粒子产生;在体外超声显像实验中,纳米粒经近红外光辐照后超声诊断仪检测到大量上扬的微泡,可增强体外超声显像的效果;体内分布实验表明,该纳米粒可因肿瘤的高渗透及滞留效应(EPR效应)在肿瘤中大量累积。本研究制备了可在肿瘤内部大量累积的纳米-微米可逆转变的超声显像纳米粒,为实现肿瘤病灶部位的超声显像同时结合光热-化学治疗提供了一种可行的方案。
Preparation of a nanoscale drug-bearing ultrasound contrast agent, the nanoparticles can be effectively distributed to the tumor deep parts, and in vitro experiments show that under elevated temperature or near-infrared light irradiation can achieve nano-micron size nano-micron conversion : Evaluation of its in vitro particle size changes, in vitro ultrasound imaging and distribution in vivo. The prepared nanoparticles were spherical. The hollow gold nanoparticle (HAu NS) could be seen in the lipid membrane. The particle size was 302 ± 5 nm and the dispersivity index was 0.195 ± 0.018. The distribution was uniform. Under the irradiation of near infrared light (1 or 2 W · cm -2), the solution containing the nanoparticles (0.2, 0.04 and 0.02 g · L -1 in HAu NS) was rapidly heated, Using the temperature control function of the laser particle size analyzer, it was found that a certain amount of micron-sized particles could be detected when the temperature was raised to about 52 ° C. In the in vitro ultrasonic imaging experiment, the nanoparticles were detected by the ultrasonic diagnostic apparatus after being irradiated by near-infrared light A large amount of microbubbles increased the effect of ultrasound imaging in vitro. In vivo experiments showed that the nanoparticles could accumulate in tumor due to the high permeability and retention effect of the tumor (EPR effect). In this study, a large number of nanometer-micron reversible transformable nanoparticles were prepared in the tumor, which provided a feasible solution for the simultaneous ultrasound imaging and photothermal-chemotherapeutic treatment.