Scopus İndeksli Yayınlar Koleksiyonu / Scopus Indexed Publications Collection

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

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Access type: Metadata onlyAuthor: search.filters.author.Uz, Metin

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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.
  • Conference Object
    Development of Functional Materials for Sirna Delivery and Neural Tissue Engineering
    (AIChE, 2015) Uz, Metin; Alsoy Altınkaya, Sacide; Mallapragada, Surya K.
    The current nonviral siRNA delivery systems in the literature face many problems such as, cellular entry, endosomal escape and efficient siRNA release. Considering this motive, we developed gold nanoparticles (AuNPs) and temperature/pH responsive pentablock copolymer based siRNA delivery systems to address these problems. The temperature and pH responsive cationic and amphiphilic pentablock copolymers, which were consisted of the temperature responsive Pluronic F127 middle block constructed by PEO-PPO-PEO ((poly(ethyleneoxide)-block-poly(propyleneoxide)-block-poly(ethyleneoxide))) blocks contributing cellular entry through temperature responsive micellization and pH responsive cationic PDEAEM (poly(2-diethylaminoethyl methacrylate)) end blocks facilitating nucleic acid condensation and endosomal escape, were used for the first time in the development of polyplex and AuNP based multicomponent siRNA delivery systems (MCSs). The results indicated that systems managed to protect siRNA from external effects, maintain the system stability, facilitate cellular entry and enhance endosomal escape. It was noted that the transfection efficiency of the MCSs, which were boosted by the presence of cleavable disulfide bond, was ~15% higher than the commercial product RNAiMax while the efficacy of polyplexes alone were similar to the RNAiMax.