Please use this identifier to cite or link to this item: https://hdl.handle.net/11147/5139
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dc.contributor.authorSevimli, Sema-
dc.contributor.authorSagnella, Sharon-
dc.contributor.authorKavallaris, Maria-
dc.contributor.authorBulmuş, Volga-
dc.contributor.authorDavis, Thomas P.-
dc.date.accessioned2017-03-23T13:47:40Z
dc.date.available2017-03-23T13:47:40Z
dc.date.issued2013-11
dc.identifier.citationSevimli, S., Sagnella, S., Kavallaris, M., Bulmuş, V., and Davis, T.P. (2013). Assessment of cholesterol-derived ionic copolymers as potential vectors for gene delivery. Biomacromolecules, 14(11), 4135-4149. doi:10.1021/bm4013088en_US
dc.identifier.issn1525-7797
dc.identifier.issn1526-4602-
dc.identifier.issn1525-7797-
dc.identifier.urihttps://doi.org/10.1021/bm4013088
dc.identifier.urihttp://hdl.handle.net/11147/5139
dc.description.abstractA library of cholesterol-derived ionic copolymers were previously synthesized via reversible addition-fragmentation chain transfer (RAFT) polymerization as 'smart' gene delivery vehicles that hold diverse surface charges. Polyplex systems formed with anionic poly(methacrylic acid-co-cholesteryl methacrylate) (P(MAA-co-CMA)) and cationic poly(dimethylamino ethyl methacrylate-co-cholesteryl methacrylate) (Q-P(DMAEMA-co-CMA)) copolymer series were evaluated for their therapeutic efficiency. Cell viability assays, conducted on SHEP, HepG2, H460, and MRC5 cell lines, revealed that alterations in the copolymer composition (CMA mol %) affected the cytotoxicity profile. Increasing the number of cholesterol moieties in Q-P(DMAEMA-co-CMA) copolymers reduced the overall toxicity (in H460 and HepG2 cells) while P(MAA-co-CMA) series displayed no significant toxicity regardless of the CMA content. Agarose gel electrophoresis was employed to investigate the formation of stable polyplexes and determine their complete conjugation ratios. P(MAA-co-CMA) copolymer series were conjugated to DNA through a cationic linker, oligolysine, while Q-P(DMAEMA-co-CMA)-siRNA complexes were readily formed via electrostatic interactions at conjugation ratios beginning from 6:1:1 (oligolysine-P(MAA-co-CMA)-DNA) and 20:1 (Q-P(DMAEMA-co-CMA)-siRNA), respectively. The hydrodynamic diameter, ζ potential and complex stability of the polyplexes were evaluated in accordance to complexation ratios and copolymer composition by dynamic light scattering (DLS). The therapeutic efficiency of the conjugates was assessed in SHEP cells via transfection and imaging assays using RT-qPCR, Western blotting, flow cytometry, and confocal microscopy. DNA transfection studies revealed P(MAA-co-CMA)-oligolysine-DNA ternary complexes to be ineffective transfection vehicles that mostly adhere to the cell surface as opposed to internalizing and partaking in endosomal disrupting activity. The transfection efficiency of Q-P(DMAEMA-co-CMA)-GFP siRNA complexes were found to be polymer composition and N/P ratio dependent, with Q-2% CMA-GFP siRNA polyplexes at N/P ratio 20:1 showing the highest gene suppression in GFP expressing SHEP cells. Cellular internalization studies suggested that Q-P(DMAEMA-co-CMA)-siRNA conjugates efficiently escaped the endolysosomal pathway and released siRNA into the cytoplasm. The gene delivery profile, reported herein, illuminates the positive and negative attributes of each therapeutic design and strongly suggests Q-P(DMAEMA-co-CMA)-siRNA particles are extremely promising candidates for in vivo applications of siRNA therapy.en_US
dc.description.sponsorshipAustralian Research Council (ARC)en_US
dc.language.isoenen_US
dc.publisherAmerican Chemical Societyen_US
dc.relation.ispartofBiomacromoleculesen_US
dc.rightsinfo:eu-repo/semantics/openAccessen_US
dc.subjectAgarose gel electrophoresisen_US
dc.subjectCell viability assaysen_US
dc.subjectCellular internalizationen_US
dc.subjectCopolymer compositionsen_US
dc.subjectGene transferen_US
dc.subjectTransfection efficiencyen_US
dc.subjectCholesterolen_US
dc.titleAssessment of cholesterol-derived ionic copolymers as potential vectors for gene deliveryen_US
dc.typeArticleen_US
dc.authoridTR181383en_US
dc.institutionauthorBulmuş, Volga-
dc.departmentIzmir Institute of Technology. Chemical Engineeringen_US
dc.identifier.volume14en_US
dc.identifier.issue11en_US
dc.identifier.startpage4135en_US
dc.identifier.endpage4149en_US
dc.identifier.wosWOS:000326955900035en_US
dc.identifier.scopus2-s2.0-84887567271en_US
dc.relation.publicationcategoryMakale - Uluslararası Hakemli Dergi - Kurum Öğretim Elemanıen_US
dc.identifier.doi10.1021/bm4013088-
dc.identifier.pmid24125032en_US
dc.relation.doi10.1021/bm4013088en_US
dc.coverage.doi10.1021/bm4013088en_US
item.openairetypeArticle-
item.openairecristypehttp://purl.org/coar/resource_type/c_18cf-
item.languageiso639-1en-
item.fulltextWith Fulltext-
item.grantfulltextopen-
item.cerifentitytypePublications-
crisitem.author.dept03.01. Department of Bioengineering-
Appears in Collections:Chemical Engineering / Kimya Mühendisliği
PubMed İndeksli Yayınlar Koleksiyonu / PubMed Indexed Publications Collection
Scopus İndeksli Yayınlar Koleksiyonu / Scopus Indexed Publications Collection
WoS İndeksli Yayınlar Koleksiyonu / WoS Indexed Publications Collection
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