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.authorRahme, Kamil
dc.contributor.authorGuo, Jianfeng
dc.contributor.authorHolmes, Justin D.
dc.contributor.authorO'Driscoll, Caitríona M.
dc.contributor.funderScience Foundation Irelanden
dc.contributor.funderIrish Research Councilen
dc.date.accessioned2018-08-03T11:49:14Z
dc.date.available2018-08-03T11:49:14Z
dc.date.issued2015-08-24
dc.date.updated2018-08-02T18:50:21Z
dc.description.abstractThe 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.description.statusPeer revieweden
dc.description.versionSubmitted Versionen
dc.format.mimetypeapplication/pdfen
dc.identifier.citationRahme, 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.2015.08.032en
dc.identifier.doi10.1016/j.colsurfb.2015.08.032
dc.identifier.endpage612en
dc.identifier.issn0927-7765
dc.identifier.journaltitleColloids and Surfaces B-Biointerfacesen
dc.identifier.startpage604en
dc.identifier.urihttps://hdl.handle.net/10468/6576
dc.identifier.volume135en
dc.language.isoenen
dc.publisherElsevieren
dc.relation.projectinfo:eu-repo/grantAgreement/SFI/SFI Research Centres/12/RC/2278/IE/Advanced Materials and BioEngineering Research Centre (AMBER)/en
dc.relation.projectIrish Research Council (Government of Ireland Postdoctoral Fellowship (GOIPD/2013/150))en
dc.relation.urihttp://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.urihttp://creativecommons.org/licenses/by-nc-nd/4.0/en
dc.subjectGold nanoparticlesen
dc.subjectPEGylationen
dc.subjectNon-viral siRNA deliveryen
dc.subjectPolyethylene glycol dilemmaen
dc.titleEvaluation of the physicochemical properties and the biocompatibility of polyethylene glycol-conjugated gold nanoparticles: a formulation strategy for siRNA deliveryen
dc.typeArticle (peer-reviewed)en
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