近红外光介导的尺寸可逆转变超声造影剂的制备及其性质  

The formulation and characterization of near infrared-mediated size reversible ultrasound contrast agent

作　　者：侯婉晴 郭晓萌 罗利华 范玉玲[2] 游剑[1] HOU Wan-qing GUO Xiao-meng LUO Li-hua FAN Yu-ling YOU Jian(College of Pharmaceutical Sciences, Zhejiang University, Hangzhou 310058, China Research Center of Life Science and Environmental Science, Harbin University of Commerce, Harbin 150028, China)

机构地区：[1]浙江大学药学院,浙江杭州310058 [2]哈尔滨商业大学生命科学与环境科学研究中心,黑龙江哈尔滨150028

出　　处：《药学学报》2017年第9期1458-1465,共8页Acta Pharmaceutica Sinica

摘　　要：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。The drug-loaded ultrasound（US） contrast nanoparticles, which can effectively accumulate in the tumor to penetrate into its deep section, were prepared. After being heated or under the near infrared（NIR） light irradiation, the size of nanoparticles would transform from nanometer-scale to micrometer-scale in vitro, which can vastly enhance the effect of US imaging. We evaluated the size changes of the nanoparticles in vitro, investigating their effect in ultrasound imaging and distribution in vivo. Liposomes containing hydrophobic modified hollow gold nanospheres（HAu NS）, doxorubicin（DOX） and perfluorohexane（PFH）, which were referred to DOX and HAu NS loaded PFH liposome（DHPL）, were prepared by thin film evaporation and ultrasonic technique. The morphology and size of DHPL were measured by transmission electron microscopy and particle size analyzer with dynamic light scattering（DLS） method. The agar gel pore model was used to investigate the enhanced effect of nanoparticles in vitro US imaging under the NIR light irradiation. The biodistribution of DHPL in 4T1 tumor-bearing mice after intravenous injection was measured by the in vivo imaging system. The DHPL were spherical at a particle size of 302 ± 5 nm and polydispersity index of 0.195 ± 0.018. The HAu NS loaded on phospholipid membrane was observed in transmission electron microscope（TEM） image. Under the NIR light irradiation（1 or 2 W·cm^（-2））, the temperature of the solution containing the DHPL（0.2, 0.04, 0.02 g·L^（-1） in terms of HAu NS） rose rapidly. And a certain amount of micrometer-sized particles could be detected by the particle size analyzer when the temperature of the analyzer was raised to 52 ℃. The abundant microbubbles, which would enhance the effect of US imaging, were detected by ultrasonic diagnostic apparatus when the nanoparticles were irradiated by NIR light in the in vitro US imaging experiment. The in vivo distribution experiment showed that the DHPL could effectively accumulate in the

关 键 词：超声造影剂 体外超声成像 全氟己烷 中空金纳米球 光热转化 相转变 

分 类 号：R943[医药卫生—药剂学]