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超声靶向微泡破裂增强恩度凝胶抑制裸鼠乳腺癌移植瘤血管生成作用

Ultrasound-targeted Microbubble Destruction for Improvement of Antiangiogenic Effects of Endostar Gel on Human Breast Cancer Xenograft Nude Mouse Models
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摘要 目的:探讨超声靶向微泡破裂对恩度凝胶瘤体内注射抑制裸鼠乳腺癌移植瘤血管生成作用的影响。方法:制备载恩度的PLGA-PEG-PLGA温度敏感型凝胶,检测恩度凝胶体外释放及超声辐照对药物释放的影响;建立荷人乳腺癌裸鼠移植瘤模型,分为模型组、恩度凝胶瘤体内注射组、恩度凝胶联合超声靶向微泡破裂组,每周治疗1次,连续3次后行肿瘤超声造影,测定肿瘤组织微血管密度,评价各种处理对肿瘤血管生成的抑制作用。结果:恩度凝胶在体外平稳释放约1周时间,超声辐照可提高恩度凝胶的释放速率;恩度凝胶瘤体内注射联合超声靶向微泡破裂处理具有明显的抑制肿瘤血管生成作用,肿瘤超声造影峰值强度及微血管密度均明显低于对照组及单纯恩度凝胶治疗组(P<0.05)。结论:恩度凝胶联合超声靶向微泡破裂可阻断肿瘤微循环,并有效控制缓释载体的药物释放速率,使更多释放药物作用于血管内皮细胞,具有明显的抑制肿瘤血管生成作用。 Objective:To investigate the influence of ultrasound-targeted microbubble destruction(UT-MD)on Endostar gel inhibiting breast cancer xenograft angiogenesis.Methods:The Endostar-loaded PLGAPEG-PLGA thermosensitive hydrogel was prepared,and the in vitro drug release with or without ultrasound exposure was detected.Human breast cancer-bearing nude mice were randomly divided into three groups:mode group,Endostar gel group and Endostar gel combined with UTMD group,and achieved treatment once a week for 3times.After treatment,the tumor contrast-enhanced ultrasonography(CEUS)was performed,and the tumor microvascular density(MVD)was calculated.Results:The Endostar gel steadily released drug for 7days,and ultrasound exposure enhanced the drug release velocity significantly.Compared with model group and Endostar gel group,the peak-intensity of CEUS and MVD in Endostar gel combined with UTMD group were the lowest.Conclusion:Ultrasound-targeted microbubbles destruction could interrupt the tumor blood circulation,control the drug release from Endostar gel,which possessed obviously antiangiogenic effects.
出处 《数理医药学杂志》 2014年第3期307-310,共4页 Journal of Mathematical Medicine
关键词 超声靶向微泡破裂 重组人血管内皮抑制素 温度敏感型凝胶 乳腺癌 血管生成 ultrasound-targeted microbubbles destruction endostar thermosensitive hydrogel breast cancer angiogenesis
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