Medarova Zdravka, Kumar Mohanraja, Ng Shu-Wing, Yang Junzheng, Barteneva Natasha, Evgenov Natalia V, Petkova Victoria, Moore Anna
Molecular Imaging Laboratory, MGH/MIT/HMS Athinoula A. Martinos Center for Biomedical Imaging, Massachusetts General Hospital and Harvard Medical School, Charlestown, MA 02129, USA.
Transplantation. 2008 Nov 15;86(9):1170-7. doi: 10.1097/TP.0b013e31818a81b2.
With the ultimate hope of finding a cure for diabetes, researches are looking into altering the genetic profile of the beta cell as a way to manage metabolic dysregulation. One of the most powerful new approaches for the directed regulation of gene expression uses the phenomenon of RNA interference.
Here, we establish the feasibility of a novel technology centered around multifunctional magnetic nanocarriers, which concurrently deliver siRNA to intact pancreatic islets and can be detected by magnetic resonance and optical imaging.
In the proof-of-principle studies described here, we demonstrate that, after in vitro incubation, magnetic nanoparticles carrying siRNA designed to target the model gene for enhanced green fluorescent protein are efficiently taken up by murine pancreatic islets, derived from egfp transgenic animals. This uptake can be visualized by magnetic resonance imaging and near-infrared fluorescence optical imaging and results in suppression of the target gene.
These results illustrate the value of our approach in overcoming the challenges associated with genetic modification of intact pancreatic islets in a clinically acceptable manner. Furthermore, an added advantage of our technology derives from the combined capability of our magnetic nanoparticles for siRNA delivery and magnetic labeling of pancreatic islets.
为了最终找到治愈糖尿病的方法,研究人员正在研究改变β细胞的基因图谱,以此作为控制代谢失调的一种方式。用于定向调控基因表达的最强大的新方法之一是利用RNA干扰现象。
在此,我们确立了一种以多功能磁性纳米载体为核心的新技术的可行性,该技术可将小干扰RNA(siRNA)同时递送至完整的胰岛,并可通过磁共振和光学成像进行检测。
在此处描述的原理验证研究中,我们证明,在体外孵育后,携带针对增强型绿色荧光蛋白模型基因设计的siRNA的磁性纳米颗粒被源自增强型绿色荧光蛋白转基因动物的小鼠胰岛有效摄取。这种摄取可以通过磁共振成像和近红外荧光光学成像观察到,并导致靶基因受到抑制。
这些结果说明了我们的方法在以临床可接受的方式克服与完整胰岛基因改造相关的挑战方面的价值。此外,我们技术的一个额外优势源于我们的磁性纳米颗粒用于siRNA递送和胰岛磁性标记的综合能力。