Abstract
Pancreatic islet transplantation is a promising therapeutic approach for type 1 diabetes.
However, recent advances in islet transplantation are limited by significant graft loss after transplantation. Multiple immunological and nonimmunological factors contribute to this loss. Novel therapies that could target the core reasons for the islet graft loss are desperately needed. Small interfering RNA can be used to inhibit the expression of virtually any gene with single-nucleotide specificity including genes responsible for islet damage. Applying adequate delivery of siRNA molecules to pancreatic islets prior to transplantation holds a great potential for improving the survival of islet grafts. Noninvasive imaging provides means for monitoring the survival of transplanted islets in real time. Here, we summarize the approach that has been developed to deliver siRNA to pancreatic islets in conjunction with tracking of the graft outcome by in vivo magnetic resonance imaging (MRI). We synthesize a nano-sized theranostic agent consisting of magnetic nanoparticles (MN), a reporter for MRI, labeled with Cy5.5 dye for near-infrared fluorescence (NIRF) imaging, and conjugated to siRNA molecule targeting genes that are harmful to islet grafts. Pre-labeling of islets by MN-Cy5.5-siRNA allowed us to monitor the survival of transplanted islet grafts by MRI and NIRF imaging and resulted in efficient silencing of the target genes in vivo. This novel approach combines a therapeutic effect provided by RNA interference technology with in vivo MR imaging and is expected to significantly improve the outcome of islet transplantation in patients with type 1 diabetes.
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References
Lebastchi J, Herold KC (2012) Immunologic and metabolic biomarkers of beta-cell destruction in the diagnosis of type 1 diabetes. Cold Spring Harb Perspect Med 2(6):a007708. doi:10.1101/cshperspect.a007708
Azzi J, Geara AS, El-Sayegh S, Abdi R (2010) Immunological aspects of pancreatic islet cell transplantation. Expert Rev Clin Immunol 6(1):111–124
Kleijwegt FS, Roep BO (2013) Infectious tolerance as candidate therapy for type 1 diabetes: transfer of immunoregulatory properties from human regulatory T cells to other T cells and proinflammatory dendritic cells. Crit Rev Immunol 33(5):415–434
Narang AS, Mahato RI (2006) Biological and biomaterial approaches for improved islet transplantation. Pharmacol Rev 58(2):194–243. doi:10.1124/pr.58.2.6
Niclauss N, Morel P, Berney T (2014) Has the gap between pancreas and islet transplantation closed? Transplantation 98(6):593–599. doi:10.1097/TP.0000000000000288
Moore A, Medarova Z (2009) Imaging of siRNA delivery and silencing. Methods Mol Biol 487:93–110. doi:10.1007/978-1-60327-547-7_5
Medarova Z, Kumar M, Ng SW, Yang J, Barteneva N, Evgenov NV, Petkova V, Moore A (2008) Multifunctional magnetic nanocarriers for image-tagged SiRNA delivery to intact pancreatic islets. Transplantation 86(9):1170–1177. doi:10.1097/TP.0b013e31818a81b2
Medarova Z, Kumar M, Ng SW, Moore A (2009) Development and application of a dual-purpose nanoparticle platform for delivery and imaging of siRNA in tumors. Methods Mol Biol 555:1–13. doi:10.1007/978-1-60327-295-7_1
Wang P, Yigit MV, Medarova Z, Wei L, Dai G, Schuetz C, Moore A (2011) Combined small interfering RNA therapy and in vivo magnetic resonance imaging in islet transplantation. Diabetes 60(2):565–571. doi:10.2337/db10-1400
Wang P, Yigit MV, Ran C, Ross A, Wei L, Dai G, Medarova Z, Moore A (2012) A theranostic small interfering RNA nanoprobe protects pancreatic islet grafts from adoptively transferred immune rejection. Diabetes 61(12):3247–3254. doi:10.2337/db12-0441
Medarova Z, Evgenov NV, Dai G, Bonner-Weir S, Moore A (2006) In vivo multimodal imaging of transplanted pancreatic islets. Nat Protoc 1(1):429–435. doi:10.1038/nprot.2006.63
Evgenov NV, Medarova Z, Dai G, Bonner-Weir S, Moore A (2006) In vivo imaging of islet transplantation. Nat Med 12(1):144–148. doi:10.1038/nm1316
Evgenov NV, Medarova Z, Pratt J, Pantazopoulos P, Leyting S, Bonner-Weir S, Moore A (2006) In vivo imaging of immune rejection in transplanted pancreatic islets. Diabetes 55(9):2419–2428. doi:10.2337/db06-0484
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Wang, P., Moore, A. (2016). In Vivo Magnetic Resonance Imaging of Small Interfering RNA Nanodelivery to Pancreatic Islets. In: Medarova, Z. (eds) RNA Imaging. Methods in Molecular Biology, vol 1372. Humana Press, New York, NY. https://doi.org/10.1007/978-1-4939-3148-4_2
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DOI: https://doi.org/10.1007/978-1-4939-3148-4_2
Publisher Name: Humana Press, New York, NY
Print ISBN: 978-1-4939-3147-7
Online ISBN: 978-1-4939-3148-4
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