Evaluation of the physicochemical properties and the biocompatibility of polyethylene glycol-conjugated gold nanoparticles: a formulation strategy for siRNA delivery

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dc.contributor.author Rahme, Kamil
dc.contributor.author Guo, Jianfeng
dc.contributor.author Holmes, Justin D.
dc.contributor.author O'Driscoll, Caitríona M.
dc.date.accessioned 2018-08-03T11:49:14Z
dc.date.available 2018-08-03T11:49:14Z
dc.date.issued 2015-08-24
dc.identifier.citation Rahme, K., Guo, J., Holmes, J. D. and O’Driscoll, C. M. (2015) 'Evaluation of the physicochemical properties and the biocompatibility of polyethylene glycol-conjugated gold nanoparticles: A formulation strategy for siRNA delivery', Colloids and Surfaces B: Biointerfaces, 135, pp. 604-612. doi: 10.1016/j.colsurfb.2015.08.032 en
dc.identifier.volume 135 en
dc.identifier.startpage 604 en
dc.identifier.endpage 612 en
dc.identifier.issn 0927-7765
dc.identifier.uri http://hdl.handle.net/10468/6576
dc.identifier.doi 10.1016/j.colsurfb.2015.08.032
dc.description.abstract The potential of RNA interference (RNAi)-based therapeutics for cancer has received much attention; however, delivery of RNAi effectors, such as small interfering RNA (siRNA), remains an obstacle to clinical translation. Non-viral delivery vectors have been used extensively to enhance siRNA delivery. Recently, the potential of gold nanoparticles (AuNPs) for transporting drugs, proteins and genetic materials has been demonstrated. Previously, our laboratory synthesised positively charged, surfactant-free AuNPs in water by the reduction of gold (III) chloride (AuCl3) using hydroxylamine hydrochloride (NH2OH·HCl) in the presence of l-cysteine methyl ester hydrochloride (HSCH2CH(NH2)COOCH3·HCl) as a capping agent. These AuNPs, which achieve higher cell viability in comparison to cetyl trimethyl ammonium bromide (CTAB, a surfactant)-capped counterparts, have demonstrated potential for siRNA delivery. However, it is well known that systemic administration of cationic delivery systems without biological stablising moieties causes non-specific binding with negatively charged serum proteins, resulting in particle aggregation and opsonisation. Consequently, highly stable AuNPs capped with l-cysteine methyl ester hydrochloride conjugated to poly(ethylene glycol) (PEG) were synthesised in this study. PEGylation enhanced the biocompatibility of the AuNPs by reducing toxicity in a range of cell types, by inhibiting interaction with serum proteins thus avoiding aggregation, and, by providing protection against degradation by nucleases. Moreover, these PEGylated AuNPs formed nanoparticles (NPs) with siRNA (which was first compacted with protamine), and had a diameter within the nanoscale range (∼250nm) and a near neutral surface charge (∼10mV). In the future a bifunctional PEG chain on the AuNPs (i.e., SH-PEG-NH2, SH-PEG-COOH) will be used to facilitate conjugation of a targeting ligand to enhance cell specific uptake. en
dc.format.mimetype application/pdf en
dc.language.iso en en
dc.publisher Elsevier en
dc.relation.uri http://www.sciencedirect.com/science/article/pii/S092777651530148X
dc.rights © 2015 Elsevier B.V. This submitted manuscript version is made available under the CC-BY-NC-ND 4.0 license. en
dc.rights.uri http://creativecommons.org/licenses/by-nc-nd/4.0/ en
dc.subject Gold nanoparticles en
dc.subject PEGylation en
dc.subject Non-viral siRNA delivery en
dc.subject Polyethylene glycol dilemma en
dc.title Evaluation of the physicochemical properties and the biocompatibility of polyethylene glycol-conjugated gold nanoparticles: a formulation strategy for siRNA delivery en
dc.type Article (peer-reviewed) en
dc.internal.authorcontactother Justin D. Holmes, Chemistry, University College Cork, Cork, Ireland. +353-21-490-3000 Email: j.holmes@ucc.ie en
dc.internal.availability Full text available en
dc.date.updated 2018-08-02T18:50:21Z
dc.description.version Submitted Version en
dc.internal.rssid 318345244
dc.contributor.funder Science Foundation Ireland en
dc.contributor.funder Irish Research Council en
dc.description.status Peer reviewed en
dc.identifier.journaltitle Colloids and Surfaces B-Biointerfaces en
dc.internal.copyrightchecked No !!CORA!! en
dc.internal.licenseacceptance Yes en
dc.internal.IRISemailaddress j.holmes@ucc.ie en
dc.relation.project info:eu-repo/grantAgreement/SFI/SFI Research Centres/12/RC/2278/IE/Advanced Materials and BioEngineering Research Centre (AMBER)/ en
dc.relation.project Irish Research Council (Government of Ireland Postdoctoral Fellowship (GOIPD/2013/150)) en


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© 2015 Elsevier B.V. This submitted manuscript version is made available under the CC-BY-NC-ND 4.0 license. Except where otherwise noted, this item's license is described as © 2015 Elsevier B.V. This submitted manuscript version is made available under the CC-BY-NC-ND 4.0 license.
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