[1]李硕阳,尹庭辉,李景果,等.载siRNA微泡实现肿瘤治疗与疗效评估一体化的可行性分析[J].南方医科大学学报,2015,(06):874.
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载siRNA微泡实现肿瘤治疗与疗效评估一体化的可行性分析()
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《南方医科大学学报》[ISSN:1673-4254/CN:44-1627/R]

卷:
期数:
2015年06期
页码:
874
栏目:
出版日期:
2015-06-15

文章信息/Info

Title:
Feasibility of integrating tumor therapy with therapeutic effect evaluation using
siRNA-loaded microbubbles
作者:
李硕阳尹庭辉李景果郑博文邱 晨王 平
关键词:
小干扰RNA脂质微泡超声造影肿瘤治疗基因治疗疗效评估
Keywords:
small interfering RNA microbubbles contrast-enhanced ultrasonography tumor therapy gene therapytherapeutic evaluation
摘要:
目的探讨利用载小干扰RNA(small interfering RNA, siRNA)的脂质微泡超声造影剂实现恶性肿瘤基因治疗与疗效评估
一体化的可行性。方法以异质性组装法制备载siRNA的脂质微泡,并用动态光散射法检测其直径大小和表面电位。通过激
光共聚焦显微镜观察红色荧光标记的siRNA在瘤内的分布。针对抗凋亡基因sirtuin 2(SIRT2)设计siRNA,通过在体实验研究
载siRNA微泡在超声辐照下的肿瘤基因沉默效果。在用载siRNA微泡治疗肿瘤的同时,以超声造影技术观察肿瘤治疗效果。
结果siRNA微泡的直径为400.7±30.5 nm,表面带弱正电(+8.8±0.8 mV)。siRNA微泡协同超声辐照能高效地将siRNA递送到
肿瘤细胞胞浆内,有效沉默肿瘤组织中的SIRT2基因,诱导肿瘤凋亡,明显减缓肿瘤的生长速度。超声造影检查结果提示,载
siRNA微泡具有良好的超声显像效果,能在治疗过程中实时评估肿瘤的血供情况。结论新型载siRNA的脂质微泡超声造影剂
在活体上能对肿瘤进行基因沉默治疗,同时观察肿瘤治疗效果,实现恶性肿瘤基因治疗与疗效评估的一体化。
Abstract:
Objective To evaluate the feasibility of integrating cancer gene therapy with therapeutic effect evaluation using
siRNA-loaded nano-scale microbubbles (siRNA-NBs). Methods siRNA-NBs were prepared by hetero-assembly of polymeric
siRNA micelles and liposomal microbubbles, and the particle sizes and surface potentials were examined with dynamic light
scattering. The distributions of cy3-labled siRNA in the tumor tissues were evaluated using confocal laser scanning
microscopy. A siRNA targeting the anti-apoptosis gene SIRT2 was designed and its gene silencing effects was tested in vivo
using siRNA-NBs with ultrasound exposure. The therapeutic effect of the loaded siRNA-NBs was evaluated by
contrast-enhanced ultrasonography. Results The siRNA-NBs had a mean diameter of 400.7 ± 30.5 nm with a weak positive
charge of +8.8±0.8 mV. With ultrasound exposure, siRNA-NBs effectively delivered cy3-siRNA into the cytoplasm of cancer
cells and caused SIRT2 suppression and cell apoptosis in tumor tissues, resulting in significantly suppressed tumor growth. In
addition, contrast-enhanced ultrasonography of siRNA-NBs provided good imaging quality to allow real-time observation of
blood supply during gene therapy. Conclusions As a novel ultrasound contrast agent, siRNA-NBs make possible the
integration of tumor gene therapy and therapeutic effect evaluation for cancer.

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更新日期/Last Update: 1900-01-01