靶向CD147纳米微泡的制备及超声成像能力检测  

Preparation and ultrasonic imaging ability of CD147-targeted nanobubbles

作　　者：袁海霞 关佩珊 金赟杰 杨萍[2] 吴爱琴 王文平 YUAN Hai-xia;GUAN Pei-shan;JIN Yun-jie;YANG Ping;WU Ai-qin;WANG Wen-ping(Department of Ultrasound,Zhongshan Hospital,Fudan University(Xiamen Branch),Xiamen 361015,Fujian,China;Department of Ultrasound,Zhongshan Hospital,Fudan University,Shanghai 200032,China;Institute of Ultrasound Medicine and Engineering,Fudan University,Shanghai 200032,China)

机构地区：[1]复旦大学附属中山医院厦门医院超声科,厦门361015 [2]复旦大学附属中山医院超声科,上海200032 [3]复旦大学超声医学与工程研究所,上海200032

出　　处：《中国临床医学》2022年第1期84-87,共4页Chinese Journal of Clinical Medicine

基　　金：福建省卫生健康科研人才项目(2019-ZQNB-39);厦门市科技计划医疗卫生项目(3502Z20184002);上海市临床重点专科项目(shslczdzk03501)。

摘　　要：目的制备靶向CD147纳米微泡造影剂,并评价其理化性质、对肝细胞肝癌(肝癌)细胞的靶向能力及超声成像能力。方法将PLGA-PEG、DSPE-PEG2000-COOH、全氟丙烷饱和水溶液混合,通过偶联反应与CD147抗体结合,制备靶向CD147纳米微泡。将靶向CD147及非靶向纳米微泡分别与MHCC-97H(肝癌细胞)共孵育,检测纳米微泡的寻靶能力。靶向CD147微泡制备后1 d及3 d检测粒径大小,并进行体外及裸鼠体内超声显像。结果制备后1 d靶向微泡粒径(188.1±4.8)nm、3 d为(193.1±11.3)nm。免疫荧光检测显示靶向CD147纳米微泡较非靶向纳米微泡可更多与MHCC-97H细胞结合(P<0.01)。制备后1 d及3 d,靶向CD147纳米微泡可均匀分布于PBS中,在裸鼠体内有较好的超声成像能力。结论制备的靶向CD147纳米微泡理化性质稳定,可与肝癌细胞特异性结合,在体外及体内均具有较好的超声成像能力,可作为一种特异结合肝癌细胞的超声分子显像及肝癌治疗的分子探针。Objective To prepare CD147-targeted nanobubble contrast agent and to evaluate its physicochemical properties, liver cancer cell-targeting ability, and ultrasound imaging ability. Methods PLGA-PEG, DSPE-PEG2000-COOH, and perfluoropropane saturated aqueous solution were mixed and combined with CD147 antibody by coupling reaction to prepare CD147-targeted nanobubbles. CD147-targeted and non-targeted nanobubbles were co-incubated with MHCC-97 H cells, respectively, and the targeting ability of nanobubbles was evaluated. The particle size of CD147-targeted microbubbles was detected at 1d and 3d after the preparation, and the ultrasonic imaging was performed in vitro and in nude mice. Results CD147-targeted nanobubbles were uniformly distributed in the solution, and immunofluorescence results showed that CD147-targeted nanobubbles bond to MHCC-97 H cells significantly more than the non-targeted nanobubbles(P<0.01). The average diameter of targeted bubbles was(188.1±4.8) nm and(193.1±11.3) nm at 1d and 3d after preparation, respectively. At the 1d and 3d, the targeted microbubbles had good ultrasound imaging ability both in vitro and in vivo. Conclusion The prepared CD147-targeted nanobubbles have stable physical and chemical properties, can specifically bind to liver cancer cells, and have good ultrasound imaging ability in vitro and in vivo. They can be used as a nano-scale molecular probe for ultrasonic molecular imaging and targeted therapy of liver cancer.

关 键 词：CD147 肝癌细胞 超声分子成像 寻靶能力 

分 类 号：R445.1[医药卫生—影像医学与核医学]