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Molecules 2017, 22(2), 231; doi:10.3390/molecules22020231

Construction and Biological Evaluation of a Novel Integrin ανβ3-Specific Carrier for Targeted siRNA Delivery In Vitro

Department of Nuclear Medicine, Peking University First Hospital, No. 8, Xishiku St., West District, Beijing 100034, China
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Academic Editor: Harri Lönnberg
Received: 31 December 2016 / Revised: 28 January 2017 / Accepted: 1 February 2017 / Published: 4 February 2017
(This article belongs to the Special Issue Synthesis and Applications of Oligonucleotide Conjugates)
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Abstract

(1) Background: The great potential of RNA interference (RNAi)-based gene therapy is premised on the effective delivery of small interfering RNAs (siRNAs) to target tissues and cells. Hence, we aimed at developing and examining a novel integrin αvβ3-specific delivery carrier for targeted transfection of siRNA to malignant tumor cells; (2) Methods: Arginine-glycine-aspartate motif (RGD) was adopted as a tissue target for specific recognition of integrin αvβ3. To enable siRNA binding, a chimeric peptide was synthesized by adding nonamer arginine residues (9R) at the carboxy terminus of cyclic-RGD dimer, designated as c(RGD)2-9R. The efficiency of 9R peptide transferring siRNA was biologically evaluated in vitro by flow cytometry, confocal microscopy, and Western blot; (3) Results: An optimal 10:1 molar ratio of c(RGD)2-9R to siRNA was confirmed by the electrophoresis on agarose gels. Both the flow cytometry and confocal microscopy results testified that transfection of c(RGD)2-9R as an siRNA delivery carrier was obviously higher than the naked-siRNA group. The results of Western blot demonstrated that these 9R peptides were able to transduce siRNA to HepG2 cells in vitro, resulting in efficient gene silencing; and (4) Conclusion: The chimeric peptide of c(RGD)2-9R can be developed as an effective siRNA delivery carrier and shows potential as a new strategy for RNAi-based gene therapy. View Full-Text
Keywords: RNA interference (RNAi); small interfering RNA (siRNA); arginine-glycine-aspartate (RGD); integrin αvβ3 RNA interference (RNAi); small interfering RNA (siRNA); arginine-glycine-aspartate (RGD); integrin αvβ3
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This is an open access article distributed under the Creative Commons Attribution License which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited. (CC BY 4.0).

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MDPI and ACS Style

Chen, X.; Liu, M.; Wang, R.; Yan, P.; Zhang, C.; Ma, C.; Yin, L. Construction and Biological Evaluation of a Novel Integrin ανβ3-Specific Carrier for Targeted siRNA Delivery In Vitro. Molecules 2017, 22, 231.

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