Researcher: Konca, Yeliz Utku
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Konca, Yeliz Utku
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Publication Metadata only Investigation of the structure-morphology property behavior of thermoplastic polyurea copolymers based on polyether and polydimethylsiloxane soft segments(Amer Chemical Soc, 2003) Atilla, GE; Ekin, A; Kurt, P; Sheth, JP; Wilkes, GL; Department of Chemistry; Department of Chemistry; Department of Chemistry; Yılgör, İskender; Yılgör, Emel; Konca, Yeliz Utku; Faculty Member; Researcher; Teaching Faculty; Department of Chemistry; College of Sciences; College of Sciences; College of Sciences; 24181; N/A; 111280Publication Metadata only pH and molecular weight dependence of auric acid reduction by polyethylenimine and the gene transfection efficiency of cationic gold nanoparticles thereof(Royal Society of Chemistry (RSC), 2018) N/A; N/A; N/A; N/A; Department of Chemistry; N/A; Department of Chemistry; Çavuşlar, Özge; Celaloğlu, Çağnur; Duman, Fatma Demir; Konca, Yeliz Utku; Yağcı, Mustafa Barış; Acar, Havva Funda Yağcı; PhD Student; Undergraduate Student; PhD Student; Teaching Faculty; Researcher; Faculty Member; Department of Chemistry; Koç University Surface Science and Technology Center (KUYTAM) / Koç Üniversitesi Yüzey Teknolojileri Araştırmaları Merkezi (KUYTAM); Graduate School of Sciences and Engineering; College of Sciences; Graduate School of Sciences and Engineering; N/A; College of Sciences; College of Sciences; N/A; N/A; N/A; N/A; 111280; N/A; 178902Small, cationic gold nanoparticles (GNP) are produced by the direct reduction of auric acid in a non-reducing solvent, water, with branched polyethylenimine (bPEI) in a broad pH range (3.0-9.0). Basic pH, which is studied for the first time, emerged as a favorable condition to achieve good reducing power and surface passivation simultaneously, providing smaller particles (hydrodynamic size ca. 6 nm) with enhanced long-term stability and a sharper surface plasmon peak (SPP). This synthetic method produces colloidal GNPs with bPEI in a broad molecular weight range (0.6, 1.8, 10 and 25 kDa). The molecular weight did not influence the crystal size much but did affect the hydrodynamic size and the stability. 0.6 kDa bPEI provides the largest GNPs (ca. 100 nm aggregates) which lack long term stability. 1.8 kDa bPEI provides small particles (hydrodynamic size ca. 7 nm) with the sharpest SPP. The GNPs prepared with 25 and 1.8 kDa bPEI show no significant cytotoxicity in HEK 293T cells and PEI25-Au transfects green fluorescent protein (GFP) into HEK 293T cells more efficiently (82%) than FuGENE (R) (50%). This simple one pot synthesis of cationic GNPs in water is a valuable, simple alternative for the generation of new cationic GNPs in water with even low molecular weight PEI.Publication Metadata only Nanometer-scale siRNA carriers incorporating peptidomimetic oligomers: physical characterization and biological activity(Dove Medical Press, 2014) Kirshenbaum, Kent; Zuckermann, Ronald N.; Department of Chemistry; Konca, Yeliz Utku; Teaching Faculty; Department of Chemistry; College of Sciences; 111280Synthetic short interfering RNA (siRNA) oligonucleotides can trigger the RNA interference pathway and lead to selective gene silencing. Despite considerable enthusiasm and investment, formidable challenges remain that may deter translating this breakthrough discovery into clinical applications. In particular, the development of efficient, nontoxic, nonimmunogenic methods for delivering siRNA in vivo has proven to be exceptionally challenging. Thorough analysis of the relationship between the structure and function of siRNA carrier systems, both in isolation and in complex with RNA, will facilitate the design of efficient nonviral siRNA delivery vehicles. In this study, we explore the relationship between the physicochemical characteristics and the biological activity of "lipitoid" compounds as potent siRNA delivery vehicles. Lipitoids are cationic peptidomimetic oligomers incorporating a peptoid and a phospholipid moiety. Lipitoids can associate with siRNA oligonucleotides and self-assemble into spherical lipitoid-based nanoparticles (LNPs), with dimensions that are dependent upon the medium and the stoichiometric ratio between the cationic monomers of the lipitoid and anionic siRNA oligonucleotides. The morphology, gene silencing efficiency, and cytotoxicity of the siRNA-loaded LNPs are similarly sensitive to the stoichiometry of the complexes. The medium in which the LNPs are formed affects the assembled cargo particles' characteristics such as particle size, transfection efficiency, and stability. Formation of the LNPs in the biological, serum-free medium OptiMEM resulted in LNPs an order of magnitude larger than LNPs formed in water, and were twice as efficient in siRNA transfection compared to LNPs formed in water. Inhibitor studies were conducted to elucidate the efficiency of lysosomal escape and the uptake mechanism of the siRNA-loaded LNPs. Our results suggest that these lipitoid-based, siRNA-loaded spherical LNPs are internalized through a lipid raft-dependent and dynamin-mediated pathway, circumventing endosomal and lysosomal encapsulation. The lipitoid-siRNA nanospheres proved to be suitable platforms for investigating the critical parameters determining the efficiency of transfection agents, revealing the necessity for conducting characterization studies in biological media. The investigation of the LNP internalization pathway points to an alternative uptake route that bypasses the lysosome, explaining the surprisingly high efficiency of LNPs and suggesting that the uptake mechanism should be probed rather than assumed for the next generation of rationally designed transfection agents.Publication Open Access Nanometer-scale siRNA carriers incorporating peptidomimetic oligomers: physical characterization and biological activity(Dove Medical Press, 2014) Kirshenbaum, Kent; Zuckermann, Ronald N.; Department of Chemistry; Konca, Yeliz Utku; Teaching Faculty; Department of Chemistry; College of Sciences; 111280Synthetic short interfering RNA (siRNA) oligonucleotides can trigger the RNA interference pathway and lead to selective gene silencing. Despite considerable enthusiasm and investment, formidable challenges remain that may deter translating this breakthrough discovery into clinical applications. In particular, the development of efficient, nontoxic, nonimmunogenic methods for delivering siRNA in vivo has proven to be exceptionally challenging. Thorough analysis of the relationship between the structure and function of siRNA carrier systems, both in isolation and in complex with RNA, will facilitate the design of efficient nonviral siRNA delivery vehicles. In this study, we explore the relationship between the physicochemical characteristics and the biological activity of "lipitoid" compounds as potent siRNA delivery vehicles. Lipitoids are cationic peptidomimetic oligomers incorporating a peptoid and a phospholipid moiety. Lipitoids can associate with siRNA oligonucleotides and self-assemble into spherical lipitoid-based nanoparticles (LNPs), with dimensions that are dependent upon the medium and the stoichiometric ratio between the cationic monomers of the lipitoid and anionic siRNA oligonucleotides. The morphology, gene silencing efficiency, and cytotoxicity of the siRNA-loaded LNPs are similarly sensitive to the stoichiometry of the complexes. The medium in which the LNPs are formed affects the assembled cargo particles' characteristics such as particle size, transfection efficiency, and stability. Formation of the LNPs in the biological, serum-free medium OptiMEM resulted in LNPs an order of magnitude larger than LNPs formed in water, and were twice as efficient in siRNA transfection compared to LNPs formed in water. Inhibitor studies were conducted to elucidate the efficiency of lysosomal escape and the uptake mechanism of the siRNA-loaded LNPs. Our results suggest that these lipitoid-based, siRNA-loaded spherical LNPs are internalized through a lipid raft-dependent and dynaminmediated pathway, circumventing endosomal and lysosomal encapsulation. The lipitoid-siRNA nanospheres proved to be suitable platforms for investigating the critical parameters determining the efficiency of transfection agents, revealing the necessity for conducting characterization studies in biological media. The investigation of the LNP internalization pathway points to an alternative uptake route that bypasses the lysosome, explaining the surprisingly high efficiency of LNPs and suggesting that the uptake mechanism should be probed rather than assumed for the next generation of rationally designed -transfection agents.