In vivo imaging of siRNA delivery and silencing in tumors
In vivo imaging of siRNA delivery and silencing in tumors
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DOI：
10.1038/nm1486
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发表时间：
2007-03-01
期刊：
影响因子：
82.9
通讯作者：
Moore, Anna
中科院分区：
文献类型：
--
作者：
Medarova, Zdravka;Pham, Wellington;Moore, Anna
随着RNA干扰（RNAi）作为一种治疗策略的潜力越来越大，迫切需要新的非侵入性方法来检测siRNA的传递和沉默。在这里，我们描述了用于siRNA体内转移的双用途探针的发展，并通过高分辨率磁共振成像（MRI）和近红外体内光学成像（NIRF）同时成像其在肿瘤中的积累。这些探针由磁性纳米颗粒组成，用近红外染料标记，并与模型或治疗靶点特异性的siRNA分子共价连接。此外，这些纳米颗粒被膜易位肽修饰，用于细胞内递送。我们展示了通过MRI和光学成像在两个单独的肿瘤模型中跟踪这些探针的肿瘤摄取的可行性。我们还使用原理验证光学成像来证实沉默过程的效率。这些研究代表了siRNA传递和成像策略进步的第一步，对于癌症治疗产品的开发和优化至关重要。
With the increased potential of RNA interference (RNAi) as a therapeutic strategy, new noninvasive methods for detection of siRNA delivery and silencing are urgently needed. Here we describe the development of dual-purpose probes for in vivo transfer of siRNA and the simultaneous imaging of its accumulation in tumors by high-resolution magnetic resonance imaging (MRI) and near-infrared in vivo optical imaging (NIRF). These probes consisted of magnetic nanoparticles labeled with a near-infrared dye and covalently linked to siRNA molecules specific for model or therapeutic targets. Additionally, these nanoparticles were modified with a membrane translocation peptide for intracellular delivery. We show the feasibility of in vivo tracking of tumor uptake of these probes by MRI and optical imaging in two separate tumor models. We also used proof-of-principle optical imaging to corroborate the efficiency of the silencing process. These studies represent the first step toward the advancement of siRNA delivery and imaging strategies, essential for cancer therapeutic product development and optimization.