Journal
TRANSPLANTATION
Volume 86, Issue 9, Pages 1170-1177Publisher
LIPPINCOTT WILLIAMS & WILKINS
DOI: 10.1097/TP.0b013e31818a81b2
Keywords
Magnetic resonance imaging; Optical imaging; RNA interference; Pancreatic islets
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Funding
- NIDDK NIH HHS [R01 DK080784, R01 DK064850, R01 DK080784-01A1, R01 DK064850-01, 5R01DK080784] Funding Source: Medline
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Background. 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. Methods. 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. Results. 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. Conclusions. 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.
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