摘要
目的构建携载CXCR4小分子拮抗剂AMD070的诊疗一体化超声靶向纳米泡,观察其在体外与乳腺癌细胞的靶向结合能力,初步探讨靶向纳米泡联合超声靶向纳米微泡破坏(ultrasound targeted nano-microbubble destruction,UTMD)对乳腺癌细胞生长的抑制作用。方法通过碳二亚胺法和机械振荡法制备携载AMD070的靶向纳米泡,检测其物理特性,观察靶向纳米泡与乳腺癌细胞的特异性结合能力,CCK-8法筛选UTMD参数并评估在体外靶向纳米泡联合UTMD对乳腺癌细胞的生长抑制作用。结果携载AMD070的超声靶向纳米泡粒径(481.72±26.17)nm,电位(-7.14±0.31)mV,其中AMD070与脂质纳米泡有效连接,体外结合实验显示靶向纳米泡相较于空白纳米泡对CXCR4阳性乳腺癌细胞有更强的亲和力,靶向纳米泡联合优化的UTMD能明显抑制CXCR4阳性的乳腺癌细胞生长。结论靶向纳米泡能与CXCR4阳性表达的乳腺癌细胞特异性结合,并在优化后UTMD的配合下显著抑制CXCR4阳性乳腺癌细胞的生长。
Objective To prepare targeted ultrasonic nanobubbles carrying small-molecule CXCR4 antagonist AMD070,which can be used in integrated diagnosis and treatment,and investigate the binding ability to breast cancer cells in vitro,in order to investigate the inhibitory effect of ultrasound targeted nanobubble destruction(UTMD)on the growth of breast cancer cells.Methods Targeted nanobubbles carrying AMD070 were prepared using the carbodiimide method and mechanical oscillation.Their particle size and zeta potential were assessed.The specific binding ability of targeted nanobubbles to breast cancer cells in vitro was evaluated.CCK-8 assay was used to optimize the parameters of UTMD and evaluate the inhibitory effect of targeted nanobubbles combined with UTMD on growth of breast cancer cells.Result The average particle size and zeta potential of ultrasonic targeted nanobubbles carrying AMD070 was 481.72±26.17 nm and-7.14±0.31 mV,respectively.AMD070 was efficiently bound to the nanobubbles.In vitro experiment showed that the targeted nanobubbles displayed stronger affinity to CXCR4 positive breast cancer cells when compared with the blank nanobubbles.When combined with UTMD,targeted nanobubbles exerted a remarkable inhibitory effect on the proliferation in CXCR4 positive breast cancer cells.Conclusion Targeted nanobubbles can specifically bind to CXCR4 positive breast cancer cells,and when combined with optimized UTMD,and the targeted nanobubbles can significantly inhibit the growth of CXCR4 positive breast cancer cells in vitro.
作者
申戴佳
朱连华
刘玉
方可敬
刘灯
郭燕丽
SHEN Daijia;ZHU Lianhua;LIU Yu;FANG Kejing;LIU Deng;GUO Yanli(Department of Ultrasonography,First Affiliated Hospital,Army Medical University(Third Military Medical University),Chongqing,400038,China)
出处
《第三军医大学学报》
CAS
CSCD
北大核心
2020年第5期473-479,共7页
Journal of Third Military Medical University
基金
国家自然科学基金面上项目(81771856)
陆军军医大学第一附属医院重大领域技术创新项目(SWH2016ZDCX4101)。
关键词
超声靶向纳米泡
诊疗一体化
CXCR4
乳腺癌
ultrasonic targeted nanobubbles
integrated diagnosis and treatment
CXCR4
breast cancer
