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

Paper ID Volume ID Publish Year Pages File Format Full-Text
5794 431 2015 7 PDF Available
Title
Improved islet transplantation outcome by the co-delivery of siRNAs for iNOS and 17β-estradiol using an R3V6 peptide carrier
Abstract

Silencing target genes such as inducible nitric oxide synthase (iNOS) using small interfering double-stranded 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 17β-estradiol (E2), which exerts anti-apoptotic effects on the islet cells. The E2-loaded R3V6 peptide micelles delivered siRNA-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.

Keywords
siRNA; iNOS; R3V6 peptide micelles; 17β-Estradiol; Islet; Transplantation
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Improved islet transplantation outcome by the co-delivery of siRNAs for iNOS and 17β-estradiol using an R3V6 peptide carrier
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Publisher
Database: Elsevier - ScienceDirect
Journal: Biomaterials - Volume 38, January 2015, Pages 36–42
Authors
, , , , , , , ,
Subjects
Physical Sciences and Engineering Chemical Engineering Bioengineering
Get Full-Text Now
Don't Miss Today's Special Offer
Price was $35.95
You save - $31
Price after discount Only $4.95
100% Money Back Guarantee
Full-text PDF Download
Online Support
Any Questions? feel free to contact us