Scopus İndeksli Yayınlar Koleksiyonu / Scopus Indexed Publications Collection

Permanent URI for this collectionhttps://hdl.handle.net/11147/7148

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Author: search.filters.author.Uz, MetinWoS Q: search.filters.wosQuartile.Q2

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  • Article
    Citation - WoS: 1
    Comparison of Cell-Penetrating and Fusogenic Tat-Ha2 Peptide Performance in Peptideplex, Multicomponent, and Conjugate Sirna Delivery Systems
    (Amer Chemical Soc, 2024) Uz, Metin; Bulmus, Volga; Altinkaya, Sacide Alsoy
    In this study, the performance of the cell-penetrating and fusogenic peptide, TAT-HA2, which consists of a cell-permeable HIV trans-activator of transcription (TAT) protein transduction domain and a pH-responsive influenza A virus hemagglutinin protein (HA2) domain, was comparatively evaluated for the first time in peptideplex, multicomponent, and conjugate siRNA delivery systems. TAT-HA2 in all three systems protected siRNA from degradation, except in the conjugate system with a low Peptide/siRNA ratio. The synergistic effect of different peptide domains enhanced the transfection efficiency of multicomponent and conjugate systems compared to that of peptideplexes, which was attributed to the surface configuration of TAT-HA2 peptides depending on the nature of attachment. Particularly, the multicomponent system showed better cellular uptake and endosomal escape than the peptideplexes, resulting in enhanced siRNA delivery in the cytoplasm. In addition, the presence of cleavable disulfide bonds in multicomponent and conjugate systems promoted the effective siRNA delivery in the cytoplasm, resulting in improved gene silencing activity. The multicomponent system reduced the level of luciferase expression in SKOV3 cells to 45% (+/- 4). In contrast, the conjugate system and the commercially available siRNA transfection agent, Lipofectamine RNAiMax, caused luciferase suppression down to 55% (+/- 2) at a siRNA dose of 100 nM. For the same dose, the peptideplex system could only reduce the luciferase expression to 65% (+/- 5). None of the developed systems showed significant toxicity at any dose. Overall, the TAT-HA2 peptide is promising as a siRNA delivery vector; however, its performance depends on the nature of attachment and, as a result, its surface configuration on the developed delivery system.
  • Article
    Citation - WoS: 65
    Citation - Scopus: 72
    Effect of Peg Grafting Density and Hydrodynamic Volume on Gold Nanoparticle-Cell Interactions: an Investigation on Cell Cycle, Apoptosis, and Dna Damage
    (American Chemical Society, 2016) Uz, Metin; Bulmuş, Volga; Alsoy Altınkaya, Sacide
    In this study, interactions of polyethylene glycol (PEG)-coated gold nanoparticles (AuNPs) with cells were investigated with particular focus on the relationship between the PEG layer properties (conformation, grafting density, and hydrodynamic volume) and cell cycle arrest, apoptosis, and DNA damage. Steric hindrance and PEG hydrodynamic volume controlled the protein adsorption, whereas the AuNP core size and PEG hydrodynamic volume were primary factors for cell uptake and viability. At all PEG grafting densities, the particles caused significant cell cycle arrest and DNA damage against CaCo2 and PC3 cells without apoptosis. However, at a particular PEG grafting density (∼0.65 chains/nm2), none of these severe damages were observed on 3T3 cells indicating discriminating behavior of the healthy (3T3) and cancer (PC3 and CaCo2) cells. It was concluded that the PEG grafting density and hydrodynamic volume, tuned with the PEG concentration and AuNP size, played an important role in particle-cell interactions.
  • Article
    Citation - WoS: 17
    Citation - Scopus: 22
    Responsive pentablock copolymers for siRNA delivery
    (Royal Society of Chemistry, 2015) Uz, Metin; Mallapragada, Surya K.; Alsoy Altınkaya, Sacide
    In this study, temperature and pH responsive cationic and amphiphilic pentablock copolymers, which consist of the temperature responsive triblock Pluronic F127 sandwiched between pH responsive PDEAEM (poly(2-diethylaminoethyl methacrylate)) end blocks, were used for the first time in the development of polyplex and gold nanoparticle (AuNP) based multicomponent siRNA delivery systems (MCSs). Copolymers in both systems protected siRNA from external effects, provided cell entry and endosomal escape. The thermoreversible micellization of the hydrophobic PPO block facilitated the cellular entry while the PDEAEM blocks enhanced the endosomal escape through protonated tertiary amine groups by pH buffering. The synergistic advantages of the different blocks showed an enhanced effect in the MCSs due to attachment and surface configuration reasons. The siRNA transfection efficiency of MCSs against luciferase expressing SKOV3 cells was 15% higher than both the polyplexes alone and the commercial siRNA transfection agent Lipofectamine RNAiMax at the same applied dose, without any toxicity. The results indicated that the multicomponent systems based on the responsive cationic pentablock copolymers and gold nanoparticles have promising potential as an efficient siRNA delivery vector for future applications.