Development of novel polymeric carriers for gene therapy için kapak resmi
Development of novel polymeric carriers for gene therapy
Development of novel polymeric carriers for gene therapy
Zelçak, Aykut, author.
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xv, 165 leaves: charts;+ 1 computer laser optical disc
The development of effective delivery systems is a limiting step in gene therapy. In this work, new linear block copolymers and star polymers were synthesized, and their siRNA delivery abilities were investigated. For this aim, diblock copolymers consisting of alternative "stealth" polymer blocks (PEG, P(OEGMA) (Poly(oligo(ethylene glycol) methyl ether methacrylate)) or P(OEtOxMA) (Poly(oligo(2-ethyl-2-oxazoline) methacrylate))); and same cationic polymer block (P(AEAEMA) (Poly(2-((2-aminoethyl)amino)ethyl methacrylate))), have been prepared via RAFT polymerization or combination of CROP and RAFT polymerizations. Additionally, to demonstrate the effect of polymeric architecture, P(OEGMA)/P(AEAEMA) miktoarm star polymers have also been synthesized via RAFT polymerization. Polymers were characterized by SEC, NMR and DLS. siRNA complexation was investigated by gel electrophoresis, DLS, SEM and TEM. Compared to star polymers, linear block copolymers could bind the siRNA molecules easier and tighter due to their more flexible natures and sterically accessible amine groups. The diameter of star polymer-siRNA complexes at N/P of 50 was found to be approximately 20 nm. Compared to this, linear block copolymers formed smaller particles (≈ 10 nm) at the same N/P ratio. The viability of linear block copolymer-treated cells was found to be 50% or better at the polymer concentration of 5 µM. In contrast, star polymers showed more detrimental effects at the same polymer concentrations. P(OEGMA)43-b-P(AEAEMA)45-siRNA complexes at N/P of 50 were taken up by 63.5% and 74.1% of H460 and Mda-mb-231 cells, respectively. In contrast, P(AEAEMA)40-b-P(OEtOxMA)38 complexes showed much lower uptake profile at the same conditions. Remarkably, P(OEGMA)43-b-P(AEAEMA)45-siRNA complexes showed potent gene silencing effect on Mda-mb-231 cells as shown by luciferase and RT-qPCR assays. Overall, it has been found that "stealth" polymers and polymeric architecture have a very significant effect on siRNA delivery.
Tek Biçim Eser Adı:
Thesis (Doctoral)--İzmir Institute of Technology:Bioengineering.

İzmir Institute of Technology: Bioengineering --Thesis (Doctoral).
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