Improved islet transplantation outcome by the co-delivery of siRNAs for iNOS and 17 beta-estradiol using an R3V6 peptide carrier

Title
Improved islet transplantation outcome by the co-delivery of siRNAs for iNOS and 17 beta-estradiol using an R3V6 peptide carrier
Authors
이민형
Keywords
siRNA; iNOS; R3V6 peptide micelles; 17β-Estradiol;; Islet; Transplantation
Issue Date
2015-01
Publisher
ELSEVIER SCI LTD
Citation
BIOMATERIALS, v. 38, Page. 36-42
Abstract
Silencing target genes such as inducible nitric oxide synthase (iNOS) using small interfering doublestranded RNA (siRNA) in islet cells has been attempted to enhance the survival of transplanted islets. However, the efficient and safe delivery of siRNA into intact islets is challenging. Here, we prepared R3V6 peptides containing a three-arginine stretch and a six-valine stretch, which form micelles with hydrophobic valine cores and cationic arginine surfaces in aqueous solution, to co-deliver siRNA and cytoprotective hydrophobic drugs to islet cells. The cationic surfaces bound to the negatively charged iNOS siRNA, and the hydrophobic core was loaded with 17 beta-estradiol (E2), which exerts anti-apoptotic effects on the islet cells. The E2-loaded R3V6 peptide micelles delivered 5iRNA-5'-FITC to mouse islets more efficiently than did Lipofectamine 2000, and without cytotoxicity. The micelle complexes containing siRNA-iNOS knocked down the expression of iNOS mRNA by ˃60% in islets and reduced cytokine-induced apoptotic cell death in vitro significantly. The delivery of siRNA-iNOS and E2 simultaneously using E2-loaded R3V6 peptide micelles improved the diabetes reversal rate of marginal mass islet transplantation into the renal subcapsular space of diabetic syngeneic mice significantly compared with the siRNA-iNOS and E2 alone treatment control groups. Our results demonstrated that the co-delivery of siRNA and a cytoprotective drug within a single non-toxic carrier, R3V6 peptide micelles, provides a novel rational strategy for combined ex vivo islet therapy to improve the outcome of islet transplantation. #C# 2014 Elsevier Ltd. All rights reserved.
URI
http://hdl.handle.net/20.500.11754/21303http://www.sciencedirect.com/science/article/pii/S0142961214011247
ISSN
0142-9612
DOI
http://dx.doi.org/10.1016/j.biomaterials.2014.10.060
Appears in Collections:
COLLEGE OF ENGINEERING[S](공과대학) > BIOENGINEERING(생명공학과) > Articles
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