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腾讯登录Sci Transl Med：新的纳米粒子缩小小鼠体内肿瘤大小
| 导读 | 通过癌症细胞的基因组测序，科学家们发现肿瘤细胞突变，删除或复制的大部分基因。这是个数据宝库，有助寻求新的药物靶标，但要想及时测试这些基因几乎是不可能的。
为了帮助加快这一进程，麻省理工学院的研究人员已经开发出了RNA纳米粒子，该技术能有助快速筛选新的药物靶标。在他们的第一项老鼠研究中，Dana-Farber癌症研究所和Broad研究院的研究人员发现，靶向ID4的纳米粒子可以缩小卵巢肿瘤。Sa... |
通过癌症细胞的基因组测序，科学家们发现肿瘤细胞突变，删除或复制的大部分基因。这是个数据宝库，有助寻求新的药物靶标，但要想及时测试这些基因几乎是不可能的。
为了帮助加快这一进程，麻省理工学院的研究人员已经开发出了RNA纳米粒子，该技术能有助快速筛选新的药物靶标。在他们的第一项老鼠研究中，Dana-Farber癌症研究所和Broad研究院的研究人员发现，靶向ID4的纳米粒子可以缩小卵巢肿瘤。Sangeeta Bhatia说这项最新研究发表在8月15日的<em>Science Translational Medicine</em>杂志上，纳米粒子系统可以缓解癌症药物开发中遇到的瓶颈问题
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哈佛医学院和论文主要作者William Hahn是医学副教授确定从国家癌症研究所癌症基因组测序项目数据库中寻找治疗癌症有前途的新靶点。那些潜在的靶点，其中许多人认为是不可用来开发药物的，蛋白质没有任何传统药物可以与之相结合的口袋。新的纳米粒子提供短链RNA可以关闭特定的基因，可能有助于科学家绕开这些不可用来开发药物的蛋白质。
在他们的第一次努力，研究人员决定把重点放在ID4基因蛋白，因为它在卵巢肿瘤中很明显高表达，但在其他类型的癌症中却并非如此。为了靶向针对ID4，Bhatia和她的学生设计了一种新类型的RNA递送纳米颗粒。这一新粒子可以穿透肿瘤靶向作用于ID4，这一点是RNA干扰技术无法实现的。在颗粒表面，粒子都是用很短的蛋白质片段标记使他们能够进入肿瘤细胞。在小鼠卵巢肿瘤的研究中，研究人员发现RNAi治疗纳米消除了大部分的肿瘤。目前研究人员正在使用该颗粒测试卵巢癌以及其他类型的癌症，包括胰脏癌其他潜在治疗靶点，他们也在寻找到ID4基因靶向微粒作为治疗卵巢癌的可能性。
编译自：<a title="" href="http://www.sciencedaily.com/releases/2012/08/120815142048.htm" target="_blank">New Nanoparticles Shrink Tumors in Mice</a>
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<a title="" href="http://dx.doi.org/10.1126/scitranslmed.3003778" target="_blank">doi:10.1126/scitranslmed.3003778</a>
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Targeted Tumor-Penetrating siRNA Nanocomplexes for Credentialing the Ovarian Cancer Oncogene ID4.
Yin Ren, Hiu Wing Cheung, Geoffrey von Maltzhan, Amit Agrawal, Glenn S. Cowley, Barbara A. Weir, Jesse S. Boehm, Pablo Tamayo, Alison M. Karst, Joyce F. Liu, Michelle S. Hirsch, Jill P. Mesirov, Ronny Drapkin, David E. Root, Justin Lo, Valentina Fogal, Erkki Ruoslahti, William C. Hahn, and Sangeeta N. Bhatia.
The comprehensive characterization of a large number of cancer genomes will eventually lead to a compendium of genetic alterations in specific cancers. Unfortunately, the number and complexity of identified alterations complicate endeavors to identify biologically relevant mutations critical for tumor maintenance because many of these targets are not amenable to manipulation by small molecules or antibodies. RNA interference provides a direct way to study putative cancer targets; however, specific delivery of therapeutics to the tumor parenchyma remains an intractable problem. We describe a platform for the discovery and initial validation of cancer targets, composed of a systematic effort to identify amplified and essential genes in human cancer cell lines and tumors partnered with a novel modular delivery technology. We developed a tumor-penetrating nanocomplex (TPN) that comprised small interfering RNA (siRNA) complexed with a tandem tumor-penetrating and membrane-translocating peptide, which enabled the specific delivery of siRNA deep into the tumor parenchyma. We used TPN in vivo to evaluate <em>inhibitor of DNA binding 4</em> (<em>ID4</em>) as a novel oncogene. Treatment of ovarian tumor–bearing mice with <em>ID4</em>-specific TPN suppressed growth of established tumors and significantly improved survival. These observations not only credential <em>ID4</em> as an oncogene in 32% of high-grade ovarian cancers but also provide a framework for the identification, validation, and understanding of potential therapeutic cancer targets.
<br/>来源：生物谷
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为了帮助加快这一进程，麻省理工学院的研究人员已经开发出了RNA纳米粒子，该技术能有助快速筛选新的药物靶标。在他们的第一项老鼠研究中，Dana-Farber癌症研究所和Broad研究院的研究人员发现，靶向ID4的纳米粒子可以缩小卵巢肿瘤。Sangeeta Bhatia说这项最新研究发表在8月15日的<em>Science Translational Medicine</em>杂志上，纳米粒子系统可以缓解癌症药物开发中遇到的瓶颈问题
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哈佛医学院和论文主要作者William Hahn是医学副教授确定从国家癌症研究所癌症基因组测序项目数据库中寻找治疗癌症有前途的新靶点。那些潜在的靶点，其中许多人认为是不可用来开发药物的，蛋白质没有任何传统药物可以与之相结合的口袋。新的纳米粒子提供短链RNA可以关闭特定的基因，可能有助于科学家绕开这些不可用来开发药物的蛋白质。
在他们的第一次努力，研究人员决定把重点放在ID4基因蛋白，因为它在卵巢肿瘤中很明显高表达，但在其他类型的癌症中却并非如此。为了靶向针对ID4，Bhatia和她的学生设计了一种新类型的RNA递送纳米颗粒。这一新粒子可以穿透肿瘤靶向作用于ID4，这一点是RNA干扰技术无法实现的。在颗粒表面，粒子都是用很短的蛋白质片段标记使他们能够进入肿瘤细胞。在小鼠卵巢肿瘤的研究中，研究人员发现RNAi治疗纳米消除了大部分的肿瘤。目前研究人员正在使用该颗粒测试卵巢癌以及其他类型的癌症，包括胰脏癌其他潜在治疗靶点，他们也在寻找到ID4基因靶向微粒作为治疗卵巢癌的可能性。
编译自：<a title="" href="http://www.sciencedaily.com/releases/2012/08/120815142048.htm" target="_blank">New Nanoparticles Shrink Tumors in Mice</a>
<div id="ztload">
<div> </div>
<div>
<div>
<img src="http://www.bioon.com/biology/UploadFiles/201208/2012081620375385.gif" alt="" width="115" height="150" border="0" />
<a title="" href="http://dx.doi.org/10.1126/scitranslmed.3003778" target="_blank">doi:10.1126/scitranslmed.3003778</a>
PMC:
PMID:
</div>
<div>
Targeted Tumor-Penetrating siRNA Nanocomplexes for Credentialing the Ovarian Cancer Oncogene ID4.
Yin Ren, Hiu Wing Cheung, Geoffrey von Maltzhan, Amit Agrawal, Glenn S. Cowley, Barbara A. Weir, Jesse S. Boehm, Pablo Tamayo, Alison M. Karst, Joyce F. Liu, Michelle S. Hirsch, Jill P. Mesirov, Ronny Drapkin, David E. Root, Justin Lo, Valentina Fogal, Erkki Ruoslahti, William C. Hahn, and Sangeeta N. Bhatia.
The comprehensive characterization of a large number of cancer genomes will eventually lead to a compendium of genetic alterations in specific cancers. Unfortunately, the number and complexity of identified alterations complicate endeavors to identify biologically relevant mutations critical for tumor maintenance because many of these targets are not amenable to manipulation by small molecules or antibodies. RNA interference provides a direct way to study putative cancer targets; however, specific delivery of therapeutics to the tumor parenchyma remains an intractable problem. We describe a platform for the discovery and initial validation of cancer targets, composed of a systematic effort to identify amplified and essential genes in human cancer cell lines and tumors partnered with a novel modular delivery technology. We developed a tumor-penetrating nanocomplex (TPN) that comprised small interfering RNA (siRNA) complexed with a tandem tumor-penetrating and membrane-translocating peptide, which enabled the specific delivery of siRNA deep into the tumor parenchyma. We used TPN in vivo to evaluate <em>inhibitor of DNA binding 4</em> (<em>ID4</em>) as a novel oncogene. Treatment of ovarian tumor–bearing mice with <em>ID4</em>-specific TPN suppressed growth of established tumors and significantly improved survival. These observations not only credential <em>ID4</em> as an oncogene in 32% of high-grade ovarian cancers but also provide a framework for the identification, validation, and understanding of potential therapeutic cancer targets.
<br/>来源：生物谷
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