Image-guided breast tumor therapy using a small interfering RNA nanodrug.
Image-guided breast tumor therapy using a small interfering RNA nanodrug.
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DOI：
10.1158/0008-5472.can-10-2070
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发表时间：
2010-10-01
期刊：
影响因子：
11.2
通讯作者：
Medarova Z
中科院分区：
文献类型：
--
作者：
Kumar M;Yigit M;Dai G;Moore A;Medarova Z
氧化铁纳米颗粒提供了一种可行的工具，用于组合成像和siRNA递送到肿瘤，激发了人们对探索适合于通过各种方式检测的不同成像和递送平台的积极兴趣。在这项研究中，我们描述了一种肿瘤靶向纳米药物（MN-EPPT-siBIRC 5）的合成和测试，该药物旨在将siRNA特异性地穿梭于人类乳腺肿瘤。该纳米药物结合肿瘤特异性抗原uMUC-1，该抗原在超过90%的人类乳腺癌中发现。MN-EPPT-siBIRC 5由超顺磁性氧化铁纳米颗粒（用于磁共振成像），染料Cy5.5（用于近红外光学成像），特异性靶向uMUC-1的肽（EPPT）和靶向肿瘤特异性抗凋亡基因BIRC 5的合成siRNA组成。人乳腺癌细胞的纳米药物摄取导致BIRC 5的显著下调。在静脉注射到皮下乳腺癌小鼠模型中后，纳米药物表现出优先的肿瘤摄取，这可以通过MRI和近红外光学成像来可视化。此外，MRI可用于在整个治疗过程中定量监测肿瘤组织中的纳米药物生物利用度。在两周内每周一次静脉注射该试剂导致在肿瘤中诱导相当程度的坏死和凋亡，转化为肿瘤生长速率的显著降低。我们的策略允许同时向肿瘤特异性递送siRNA和递送过程的成像。更广泛地说，它说明了将这种方法应用于许多人类癌症研究的潜力，包括基础肿瘤生物学和治疗。
Iron oxide nanoparticles offer a feasible tool for combined imaging and delivery of siRNA to tumors, stimulating active interest in exploring different imaging and delivery platforms suitable for detection by a variety of modalities. In this study we describe the synthesis and testing of a tumor-targeted nanodrug (MN-EPPT-siBIRC5) that is designed to specifically shuttle siRNA to human breast tumors. The nanodrug binds the tumor-specific antigen uMUC-1, which is found on over 90% of human breast adenocarcinomas. MN-EPPT-siBIRC5 consists of superparamagnetic iron oxide nanoparticles (for magnetic resonance imaging), the dye Cy5.5 (for near-infrared optical imaging), peptides (EPPT) that specifically target uMUC-1, and a synthetic siRNA that targets the tumor-specific anti-apoptotic gene BIRC5. Nanodrug uptake by human breast adenocarcinoma cells resulted in a significant downregulation of BIRC5. Following intravenous delivery into subcutaneous mouse models of breast cancer, the nanodrug demonstrated a preferential tumor uptake, which could be visualized by MRI and near-infrared optical imaging. Furthermore, MRI could be employed to quantitatively monitor nanodrug bioavailability in the tumor tissue throughout the course of treatment. Intravenous injection of the agent once a week over two weeks resulted in the induction of considerable levels of necrosis and apoptosis in the tumors translating into a significant decrease in tumor growth rate. Our strategy permits the simultaneous tumorspecific delivery of siRNA to tumors and the imaging of the delivery process. More generally, it illustrates the potential to apply this approach to many human cancer studies, including for basic tumor biology and therapy.