WoS İndeksli Yayınlar Koleksiyonu / WoS Indexed Publications Collection
Permanent URI for this collectionhttps://hdl.handle.net/11147/7150
Browse
3 results
Search Results
Article Citation - WoS: 34Doxorubicin Conjugated, Crosslinked, Pegylated Particles Prepared Via One-Pot Thiol-Ene Modification of a Homopolymer Scaffold: Synthesis and in Vitro Evaluation(Royal Society of Chemistry, 2011) Wong, Lingjiun; Bulmuş Zareie, Volga; Kavallaris, Maria; Bulmuş, Volga; 03.01. Department of Bioengineering; 03. Faculty of Engineering; 01. Izmir Institute of TechnologyDoxorubicin (Dox)-conjugated, poly(ethylene glycol) (PEG) shielded, reversibly crosslinked particles were prepared by a one-pot thiol-ene reaction from a RAFT-synthesized well-defined homopolymer scaffold, poly(pyridyldisulfide ethylmethacrylate) (PPDSM). Dox and PEG modified with maleimide end-groups (mal-Dox and mal-PEG), were covalently attached in one pot to free thiol groups of PPDSM (M-n = 8900 g mol(-1) and PDI = 1.18) in the presence of a disulfide reducing agent. similar to 50% of the total pyridyldisulfide units were conjugated with Dox and PEG (with an equal mol ratio). Particles with an average hydrodynamic diameter of 192 +/- 28 nm were observed to form after conjugation. Incubation of these particles with a disulfide reducing agent resulted in the disassociation of the particles. The release of Dox from the particles was pH dependent. The Dox-conjugated PEGylated particles (with a Dox content of 8 wt%) inhibited the viability of human cervical carcinoma cells (HeLa) with an IC50 value of 8 X 10(-7) M, determined by an Alamar Blue assay, while the IC50 of free Dox was 1 X 10(-7) M. The fluorescence microscopy analyses of the HeLa cells after incubation with the particles for varying times showed that the Dox carried by the particles is taken up efficiently by the cells.Article Citation - WoS: 31Citation - Scopus: 32Synthesis, Self-Assembly and Stimuli Responsive Properties of Cholesterol Conjugated Polymers(Royal Society of Chemistry, 2012) Sevimli, Sema; Bulmuş Zareie, Volga; Kavallaris, Maria; Bulmuş, Volga; Davis, Thomas P.; 03.01. Department of Bioengineering; 03. Faculty of Engineering; 01. Izmir Institute of TechnologyReversible addition-fragmentation chain transfer (RAFT) polymerization was used to generate well-defined pH-responsive biofunctional polymers as potential 'smart' gene delivery systems. A series of five poly(dimethylamino ethyl methacrylate-co-cholesteryl methacrylate) P(DMAEMA-co-CMA) statistical copolymers, with similar molecular weights and varying cholesterol content, were prepared. The syntheses, compositions and molecular weight distributions for P(DMAEMA-co-CMA) were monitored by nuclear magnetic resonance (NMR), solid-state NMR and gel permeation chromatography (GPC) evidencing well-defined polymeric structures with narrow polydispersities. Aqueous solution properties of the copolymers were investigated using turbidimetry and light scattering to determine hydrodynamic diameters and zeta potentials associated with the phase transition behaviour of P(DMAEMA-co-CMA) copolymers. UV-Visible spectroscopy was used to investigate the pH-responsive behaviour of copolymers. Hydrodynamic radii were measured in the range 10-30 nm (pH, temperature dependent) by dynamic light scattering (DLS). Charge studies indicated that P(DMAEMA-co-CMA) polymers have an overall cationic charge, mediated by pH. Potentiometric studies revealed that the buffering capacity and pK a values of polymers were dependent on cholesterol content as well as on cationic charge. The buffering capacity increased with increasing charge ratio, overall demonstrating transitions in the pH endosomal region for all five copolymeric structures. Cell viability assay showed that the copolymers displayed increasing cytotoxicity with decreasing number of cholesterol moieties. These preliminary results show the potential of these well-defined P(DMAEMA-co-CMA) polymers as in vitro siRNA delivery agents.Article Citation - WoS: 22Citation - Scopus: 25The Endocytic Pathway and Therapeutic Efficiency of Doxorubicin Conjugated Cholesterol-Derived Polymers(Royal Society of Chemistry, 2015) Sevimli, Sema; Bulmuş Zareie, Volga; Macmillan, Alexander; Whan, Renee; Kavallaris, Maria; Bulmuş, Volga; Davis, Thomas P.; 03.01. Department of Bioengineering; 03. Faculty of Engineering; 01. Izmir Institute of TechnologyPreviously synthesized poly(methacrylic acid-co-cholesteryl methacrylate) P(MAA-co-CMA) copolymers were examined as potential drug delivery vehicles. P(MAA-co-CMA) copolymers were fluorescently labelled and imaged in SHEP and HepG2 cells. To understand their cell internalization pathway endocytic inhibition studies were conducted. It was concluded that P(MAA-co-CMA) are taken up by the cells via clathrin-independent endocytosis (CIE) (both caveolae mediated and cholesterol dependent endocytosis) mechanisms. The formation and characterization of P(MAA-co-CMA)-doxorubicin (DOX) nanocomplexes was investigated by fluorescence lifetime imaging microscopy (FLIM), UV-Visible spectroscopy (UV-Vis) and dynamic light scattering (DLS) studies. The toxicity screening between P(MAA-co-CMA)-DOX nanocomplexes (at varying w/w ratios) and free DOX, revealed nanocomplexes to exhibit higher cytotoxicity towards cancer cells in comparison to normal cells. FLIM and confocal microscopy were employed for investigating the time-dependent release of DOX in SHEP cells and the cellular uptake profile of P(MAA-co-CMA)-DOX nanocomplexes in cancer and normal cell lines, respectively. The endocytic pathway of P(MAA-co-CMA)-DOX nanocomplexes were examined in SHEP and HepG2 cells via flow cytometry revealing the complexes to be internalized through both clathrin-dependent (CDE) and CIE mechanisms. The drug delivery profile, reported herein, illuminates the specific endocytic route and therapeutic efficiency of P(MAA-co-CMA)-DOX nanocomplexes strongly suggesting these particles to be promising candidates for in vivo applications.