Multifunctional magnetic nanocarriers for image-tagged SiRNA delivery to intact pancreatic islets.
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.
Medarova
Zdravka
Z
Molecular Imaging Laboratory, MGH/MIT/HMS Athinoula A. Martinos Center for Biomedical Imaging, Massachusetts General Hospital and Harvard Medical School, Charlestown, MA 02129, USA.
Kumar
Mohanraja
M
Ng
Shu-Wing
SW
Yang
Junzheng
J
Barteneva
Natasha
N
Evgenov
Natalia V
NV
Petkova
Victoria
V
Moore
Anna
A
D000818:Animals; D003920:Diabetes Mellitus / Q000628:therapy; D016503:Drug Delivery Systems / Q000379:methods*; D005290:Ferric Compounds; D005786:Gene Expression Regulation; D015316:Genetic Therapy / Q000379:methods; D049452:Green Fluorescent Proteins / Q000235:genetics / Q000378:metabolism; D007515:Islets of Langerhans / Q000378:metabolism* / Q000473:pathology*; D016381:Islets of Langerhans Transplantation; D008279:Magnetic Resonance Imaging; D008280:Magnetics; D051379:Mice; D008822:Mice, Transgenic; D023421:Models, Animal; D053758:Nanoparticles / Q000008:administration & dosage*; D034622:RNA Interference; D034741:RNA, Small Interfering / Q000008:administration & dosage*; D015203:Reproducibility of Results
D005290:Ferric Compounds; D034741:RNA, Small Interfering; C485184:enhanced green fluorescent protein; D049452:Green Fluorescent Proteins; C000499:ferric oxide