Wang, F, Shen, Y, Huang, Q et al. (3 more authors) (2015) Efficient RNA delivery by integrin-targeted glutathione responsive polyethyleneimine capped gold nanorods. Acta Biomaterialia, 23. 136 - 146 (11). ISSN 1742-7061
Abstract
RNA interference (RNAi) mediated gene silencing holds significant promises in gene therapy. A major obstacle to efficient RNAi is the systemic delivery of the therapeutic RNAs into the cytoplasmon without being trapped in intracellular endo-/lyso-somes. Herein we report the development of a PEGylated, RGD peptide modified, and disulfide cross-linked short polyethylenimines (DSPEIs) functionalized gold nanorod (RDG) for targeted small hairpin (sh)RNA delivery. The RDG effectively condensed shRNAs into stable nanoparticles, allowing for highly specific targeting of model human brain cancer cells (U-87 MG-GFP) via the v 3 integrins-mediated endocytosis. The combined effects of endosomal escape (via the proton-sponge effect of the PEIs) and efficient cleavage of the disulfide-cross-linked DSPEIs by the high intracellular glutathione content triggered rapid cytoplasma shRNAs release resulted in excellent RNAi efficiency and low cytotoxicity. Furthermore, the high stability and prolonged blood circulation afforded by PEGylation allowed for highly effective, targeted tumor accumulation and internalization of the carriers, resulting in outstanding intra-tumor gene silencing efficiency in U-87 MG-GFP tumor bearing BALB/c mice. Combining the capabilities of both passive and active targeting, intracellular glutathione-triggered "off-on" release and endosomal escape, the RDG nanocarrier developed herein appears to be a highly promising non-viral vector for efficient RNAi.
Metadata
Item Type: | Article |
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Authors/Creators: |
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Copyright, Publisher and Additional Information: | © 2015, Elsevier. This is an author produced version of a paper published in Acta Biomaterialia. Uploaded in accordance with the publisher's self-archiving policy. |
Keywords: | gold nanorod; shRNA delivery; triggered release; in vivo therapy; polyethylene imine |
Dates: |
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Institution: | The University of Leeds |
Academic Units: | The University of Leeds > Faculty of Engineering & Physical Sciences (Leeds) > School of Chemistry (Leeds) > Inorganic Chemistry (Leeds) |
Funding Information: | Funder Grant number European Research Council 331281 EU - European Union 331281 EU - European Union 331281 |
Depositing User: | Symplectic Publications |
Date Deposited: | 02 Jun 2015 11:06 |
Last Modified: | 16 Nov 2016 09:25 |
Published Version: | http://dx.doi.org/10.1016/j.actbio.2015.05.028 |
Status: | Published |
Publisher: | Elsevier |
Identification Number: | 10.1016/j.actbio.2015.05.028 |
Open Archives Initiative ID (OAI ID): | oai:eprints.whiterose.ac.uk:86594 |