Li Wenjuan, Zhang Lingping, Zhu Yuanfang, Zhang Jinyi, Shen Li, Huang Shuying, Fang Shanyu
Department of Obstetrics and Gynaecology, Wuxi Maternal and Child Health Hospital, Wuxi, 214002, Jiangshu, People's Republic of China.
Department of Obstetrics and Gynaecology, Shenzhen Baoan Maternal and Child Health Hospital, Shenzhen, 518133, Guangdong, People's Republic of China.
Arch Gynecol Obstet. 2016 Sep;294(3):631-8. doi: 10.1007/s00404-016-4092-z. Epub 2016 Apr 13.
Our previous study used freeze-drying and biotin-avidin binding methods and obtained nontargeted nanobubbles (N-NBs) and ovarian cancer-targeting nanobubbles (LHRH-NBs, luteinizing hormone-releasing hormone nanobubbles). Our study also identified the physical and chemical properties of these two contrast agents, and validated the targeting ability and underlying mechanisms of LHRH-NBs in vitro. The present study investigated the imaging of N-NBs and LHRH-NBs in nude mice and their binding with tissues.
The nude mice models of xenografts were divided into three groups, N-NB, LHRH-NB, and SonoVue. These contrast agents were injected via the caudal vein to observe the imaging of ovarian cancer. Fluorescence microscope was used to observe the penetration of N-NBs and LHRH-NBs through the vascular endothelial gaps. Immunofluorescence was used to observe the penetration of N-NBs and LHRH-NBs through vascular endothelial gaps and binding to the tumor cells.
The imaging intensity and duration were not significantly different between N-NBs and LHRH-NBs. The imaging intensity in the N-NB and LHRH-NB groups was not significantly different compared with the SonoVue group; however, the imaging duration in the N-NB and LHRH-NB groups was significantly longer than in the SonoVue group (P < 0.001). Both N-NBs and LHRH-NBs penetrated through the vascular endothelial gaps. After penetrating through the vascular endothelial gapes, LHRH-NBs could target and bind to the tumor cells.
N-NBs and LHRH-NBs are of good imaging effectiveness and relatively long imaging duration. LHRH-NB is a potent contrast agent for imaging ovarian cancer, while achieving targeted delivery of drugs to the site of ovarian cancer.
我们之前的研究采用冷冻干燥和生物素-抗生物素蛋白结合方法,获得了非靶向纳米气泡(N-NBs)和卵巢癌靶向纳米气泡(LHRH-NBs,促黄体生成素释放激素纳米气泡)。我们的研究还确定了这两种造影剂的物理和化学性质,并在体外验证了LHRH-NBs的靶向能力及其潜在机制。本研究调查了N-NBs和LHRH-NBs在裸鼠体内的成像情况及其与组织的结合情况。
将异种移植裸鼠模型分为三组,即N-NB组、LHRH-NB组和声诺维组。通过尾静脉注射这些造影剂以观察卵巢癌的成像情况。使用荧光显微镜观察N-NBs和LHRH-NBs通过血管内皮间隙的渗透情况。采用免疫荧光法观察N-NBs和LHRH-NBs通过血管内皮间隙的渗透情况以及与肿瘤细胞的结合情况。
N-NBs和LHRH-NBs的成像强度和持续时间无显著差异。N-NB组和LHRH-NB组的成像强度与声诺维组相比无显著差异;然而,N-NB组和LHRH-NB组的成像持续时间明显长于声诺维组(P<0.001)。N-NBs和LHRH-NBs均能穿透血管内皮间隙。穿透血管内皮间隙后,LHRH-NBs能够靶向并结合肿瘤细胞。
N-NBs和LHRH-NBs具有良好的成像效果和相对较长的成像持续时间。LHRH-NB是一种用于卵巢癌成像的有效造影剂,同时可实现药物向卵巢癌部位的靶向递送。