心肌特异性导向肽靶向诊疗造影剂增强心肌分子显影及其在大鼠体内的分布  

Enhancement of myocardial molecular imaging and distribution in rats of cardiomyocyte-specific homing peptide-targeted theranostic contrast agents in vivo

作　　者：赵雪丽 罗文 王志刚[2] 冉海涛[2] 刘丽文 ZHAO Xueli;LUO Wen;WANG Zhigang;RAN Haitao;LIU Liwen(Department of Sonography,the First Affiliated Hospital of Air Force Medical University,Xi＇an 710032,China;Institute of Ultrasound Imaging,Chong Qing Medical University,Chongqing 400010,China)

机构地区：[1]空军军医大学第一附属医院超声科,陕西西安710032 [2]重庆医科大学超声影像学研究所,重庆400010

出　　处：《中国医学影像技术》2018年第8期1131-1136,共6页Chinese Journal of Medical Imaging Technology

基　　金：国家国际科技合作专项(2014DFA31980);国家科学自然基金面上项目(81671693);国家重大科研仪器设备研究专项(81227801)

摘　　要：目的制备心肌特异性靶向肽(PCM)修饰的载药纳米诊疗探针,探讨其心肌靶向显影能力及其在大鼠体内的分布情况。方法采用双乳化法及碳二亚胺法制备PCM靶向载卡维地洛纳米诊疗探针(PCM/C-PFPs),检测其基本性质、大鼠体内显影及体内分布情况。结果PCM/C-PFPs纳米探针呈球形,平均粒径为(415.00±6.24)nm,电位为(-20.27±1.55)mV;包封率为(78.23±3.45)%;C-PFPs与多肽PCM连接率为(98.98±1.02)%。加热至约60℃时,该探针发生明显相变,并产生大量微气泡。声诺维组和PCM/C-PFPs+低频聚焦超声(LIFU)组大鼠心脏超声显影效果明显,但声诺维组显影仅维持数分钟,而PCM/C-PFPs+LIFU组心脏超声信号可持续至1h,且心脏显影的声强度高于其他各组(P均<0.05)。PCM/C-PFPs+LIFU组大鼠心脏切片中可见大量聚集的红色探针,明显多于C-PFPs+LIFU组和单纯PCM/C-PFPs组,且多于该组其他组织(肝、肾、肺、脾)。结论本研究成功制备的心肌靶向诊疗造影剂,具有良好的靶向心脏超声显影和大鼠体内分布特性。Objective To prepare a kind of cardiomyocyte-specific homing peptide（PCM）-targeted and drug-loaded perfluorocarbon（PFP）theranostic nanoprobes,and to explore the ability for targeting myocardial imaging and in vivo distribution in rats.Methods PCM-targeted theranostic nanoprobes loaded with carvedilol（PCM/C-PFPs）were prepared with double emulsification evaporation method combined with carbodiimide method.Then the general properties,imaging enhancement and in vivo distribution in rats were assessed.Results The nanoprobes of PCM/C-PFPs were spherical,with the average particle size of（415.00±6.24）nm and Zeta potential of（-20.27±1.55）mV.The encapsulation efficiency was（78.23±3.45）%,and the coupling efficiency of PCM and C-PFPs was（98.98±1.02）%.When heated to about60℃,obvious phase change and a large number of micro-bubbles were observed under microscope.SonoVue group and PCM/C-PFPs＋low intensity of focused ultrasound（LIFU）group showed significant imaging enhancement,in SonoVue group only maintained for several minutes,while in PCM/C-PFPs＋LIFU group kept for more than 1 h.The ultrasound intensities of heart imaging in PCM/C-PFPs＋LIFU group were significantly higher than those in other 3 groups（all P〈0.05）.A large number of red probes were found in PCM/C-PFPs＋LIFU group,more abundant than in C-PFPs＋LIFU group and PCM/C-PFPs group in the frozen sections of the heart,and significantly more than other tissues in rats of PCM/C-PFPs＋ LIFU group.Conclusion The cardiomyocyte-targeted drug-loaded theranostic nanoprobes are prepared successfully with good sonographic imaging and in vivo distribution in rats,which can be used for specific diagnosis and targeted therapy for heart diseases.

关 键 词：纳米探针 造影剂 心脏靶向 超声检查 体内分布 卡维地洛 

分 类 号：R445.1[医药卫生—影像医学与核医学]