苏琳,贾丹,许晓华,胡聪,黄菊,谭筱林,贾亦真,王志刚,任建丽.载盐酸阿霉素液态氟碳脂质体对乳腺癌治疗效果[J].中国医学影像技术,2019,35(11):1627~1631
载盐酸阿霉素液态氟碳脂质体对乳腺癌治疗效果
Treatment of breast cancer with adriamycin hydrochloride-loaded liquid fluorocarbon liposomes
投稿时间:2018-12-26  修订日期:2019-09-19
DOI:10.13929/j.1003-3289.201812144
中文关键词:  乳腺肿瘤  液态氟碳  脂质体  超声检查
英文关键词:breast neoplasms  liquid fluorocarbon  liposomes  ultrasonography
基金项目:深圳市科创委基金(JCYJ20160429185900035)、深圳市卫生计生系统科研项目(201607032)。
作者单位E-mail
苏琳 香港大学深圳医院超声科, 广东 深圳 518053  
贾丹 香港大学深圳医院超声科, 广东 深圳 518053  
许晓华 香港大学深圳医院超声科, 广东 深圳 518053 xuxh@hku-szh.org;sulin100@163.com 
胡聪 重庆医科大学超声影像学研究所, 重庆 400010  
黄菊 重庆医科大学超声影像学研究所, 重庆 400010  
谭筱林 香港大学深圳医院超声科, 广东 深圳 518053  
贾亦真 香港大学深圳医院超声科, 广东 深圳 518053  
王志刚 重庆医科大学超声影像学研究所, 重庆 400010  
任建丽 重庆医科大学超声影像学研究所, 重庆 400010  
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中文摘要:
      目的 制备一种载盐酸阿霉素(DOX)和液态氟碳(PFH)脂质体(Lip-PFH-DOX),探讨Lip-PFH-DOX纳米粒增强超声显影及对人乳腺癌MAD-MB-231细胞治疗效果。方法 采用薄膜水化法及声振法技术制备Lip-PFH-DOX纳米粒。检测Lip-PFH-DOX纳米粒的形态、粒径、电位、包封率。通过低强度聚焦超声促使纳米粒发生相变并使其破裂,通过高效液相色谱法检测不同时间点药物释放情况。检测该纳米粒对人乳腺癌MDA-MB-231的细胞毒性作用,观察细胞凋亡情况。建立裸鼠人乳腺癌MDA-MB-231模型,经尾静脉注射适量纳米粒,以低强度聚焦超声辐照,观察肿瘤部位增强超声表现。结果 成功制备载DOX和PFH的脂质体,其粒径(340.81±68.54)nm,电位(-17.72±7.66)mV,药物包封率(86.80±2.55)%。透射电镜下可观察其内部成功包载药物,光镜下可见脂质体大小均匀,可发生相变。Lip-PFH-DOX在48 h时DOX释放率达40.05±3.22,当Lip-PFH-DOX纳米粒浓度为100 μg/ml,孵育48 h时,细胞存活率为45.00%,且出现大量凋亡细胞。Lip-PFH-DOX纳米粒在低强度超声辐照后可以明显增强体内超声显影。结论 本研究成功制备了包裹DOX和PFH纳米粒,可实现体内外超声显影,同时可对MAD-MB-231细胞产生杀伤作用。
英文摘要:
      Objective To prepare the liposomes carrying doxorubicin hydrochloride (DOX) and liquid fluorocarbon (PFH) in liquid form based liposomes (Lip-PFH-DOX), and to investigate the Lip-PFH-DOX nanoparticle enhanced ultrasound imaging and its therapeutic effect on human breast cancer MAD-MB-231 cells. Methods Lip-PFH-DOX nanoparticles were prepared by using biocompatible phospholipid mixture as film-forming material and lipophilic DOX as additive. The morphology, particle size, potential and encapsulation efficiency of Lip-PFH-DOX nanoparticles were tested. Low intensity focused ultrasound was used to induce phase transition and rupture of nanoparticles. High performance liquid chromatography was used to detect drug release at different time points. The cytotoxic effect of the nanoparticles on human breast cancer MDA-MB-231 cells was detected and the apoptosis was observed. A nude mouse breast cancer mda-mb-231 model was established, and an appropriate amount of nanoparticles were injected into the tail vein to observe the enhanced ultrasound at the tumor site. Results The liposomes loaded with DOX and PFH were successfully prepared. The particle size was (340.81±68.54)nm, the potential was (-17.72±7.66)mV, and the drug encapsulation rate was (86.80±2.55)%. Under transmission electron microscopy, the drug was successfully encapsulated in the liposomes. Under light microscopy, the liposomes were uniform in size, and the phase transition was occured. In vitro, the release rate of DOX of Lip-PFH-DOX reached 40.05±3.22 at 48 h. After 48 h, when the concentration was 100 μg/ml of Lip-PFH-DOX, the survival rate decreased to 45.00%. Lip-PFH-DOX and the nanoparticles can significantly enhance ultrasound development in vivo after low intensity ultrasound irradiation. Conclusion The nanoparticles of DOX and PFH was successfully prepared, which can achieve ultrasound development in vivo and in vitro, and DOX can kill MAD-MB-231 cells.
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