- Title
- Peptide-based targeted polymeric nanoparticles for siRNA delivery
- Creator
- Hussein, Waleed M.; Cheong, Yee S.; Liu, Chang; Liu, Genan; Begum, Anjuman Ara; Attallah, Maria Adly; Moyle, Peter M.; Torchilin, Vladimir P.; Smith, Roger; Toth, Istvan
- Relation
- NHMRC.1126795 http://purl.org/au-research/grants/nhmrc/1126795
- Relation
- Nanotechnology Vol. 30, Issue 41, no. 415604
- Publisher Link
- http://dx.doi.org/10.1088/1361-6528/ab313d
- Publisher
- Institute of Physics Publishing Ltd. (IOP)
- Resource Type
- journal article
- Date
- 2019
- Description
- The development of polymer-based nanoparticulate delivery systems for siRNA is important for the clinical success of gene therapy. However, there are some major drawbacks that need to be overcome. Short interfering RNA (siRNA) has been investigated as a potential therapeutic drug to silence disease-associated genes, but its usage is limited due to the lack of effective and safe nanocarriers. In this study, DOPE-PEI, a nanoparticle consisting of the fusogenic lipid 1,2-dioleoyl-sn-glycero-3-phosphoethanolamine (DOPE) conjugated with low-molecular-weight, 600 Da, branched polyethylenimine (PEI) was produced and optimized for siRNA delivery. This delivery system was modified with other components such as 1,2-dioleoyl-sn-glycerol-3-phosphoethanolamine-N-[methoxy(polyethyleneglycol)2000] (DOPE-PEG2K), DOPE-PEG3.4K-bombesin and 1,2-dioleoyl-sn-glycerol-3-phosphoethanolamine/1,2-dioleoyl-3-trimethylammonium-propane (DOPE/DOTAP) and tested on PC-3 cells. The conjugation of DOPE to PEI polymer (DOPE-PEI) improved the efficiency of PEI to deliver siRNA into the cytosol and knockdown genes, but demonstrated high toxicity. The addition of DOPE-PEG2K reduced cellular toxicity by masking the surface positive charge of the DOPE-PEI/siRNA complex, with the incorporation of a gastrin-releasing peptide receptor (GRPR) targeting peptide and DOPE/DOTAP components improving the cellular uptake of siRNA into targeted cells and the siRNA knockdown efficiency.
- Subject
- polyethylenimine; targeting peptide; conjugation reaction; PC-3 cells; polyethyleneglycol linker; siRNA delivery
- Identifier
- http://hdl.handle.net/1959.13/1463875
- Identifier
- uon:46861
- Identifier
- ISSN:1361-6528
- Language
- eng
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