Scopus İndeksli Yayınlar Koleksiyonu / Scopus Indexed Publications Collection
Permanent URI for this collectionhttps://hdl.handle.net/11147/7148
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Article Citation - Scopus: 13Her2-Targeted, Degradable Core Cross-Linked Micelles for Specific and Dual Ph-Sensitive Dox Release(John Wiley and Sons Inc, 2022) Bayram, N.N.; Ulu, G.T.; Topuzoğulları, M.; Baran, Y.; Dinçer, İşoğlu, S.Here, a targeted, dual-pH responsive, and stable micelle nanocarrier is designed, which specifically selects an HER2 receptor on breast cancer cells. Intracellularly degradable and stabilized micelles are prepared by core cross-linking via reversible addition−fragmentation chain-transfer (RAFT) polymerization with an acid-sensitive cross-linker followed by the conjugation of maleimide–doxorubicin to the pyridyl disulfide-modified micelles. Multifunctional nanocarriers are obtained by coupling HER2-specific peptide. Formation of micelles, addition of peptide and doxorubicin (DOX) are confirmed structurally by spectroscopical techniques. Size and morphological characterization are performed by Zetasizer and transmission electron microscope (TEM). For the physicochemical verification of the synergistic acid-triggered degradation induced by acetal and hydrazone bond degradation, Infrared spectroscopy and particle size measurements are used. Drug release studies show that DOX release is accelerated at acidic pH. DOX-conjugated HER2-specific peptide-carrying nanocarriers significantly enhance cytotoxicity toward SKBR-3 cells. More importantly, no selectivity toward MCF-10A cells is observed compared to HER2(+) SKBR-3 cells. Formulations cause apoptosis depending on Bax and Caspase-3 and cell cycle arrest in G2 phase. This study shows a novel system for HER2-targeted therapy of breast cancer with a multifunctional nanocarrier, which has higher stability, dual pH-sensitivity, selectivity, and it can be an efficient way of targeted anticancer drug delivery. © 2021 Wiley-VCH GmbHArticle Citation - WoS: 38Citation - Scopus: 38Ph- and Temperature-Responsive Amphiphilic Diblock Copolymers of 4-Vinylpyridine and Oligoethyleneglycol Methacrylate Synthesized by Raft Polymerization(Elsevier Ltd., 2014) Topuzogulları, Murat; Bulmuş Zareie, Volga; Bulmuş, Volga; Dalgakıran, Eray; Dinçer, SevilDiblock copolymers of 4-vinylpyridine (4VP) and oligoethyleneglycol methyl ether methacrylate (OEGMA) were synthesized for the first time using RAFT polymerization technique as potential drug delivery systems. Effects of the number of ethylene glycol units in OEGMA, chain length of hydrophobic P4VP block, pH, concentration and temperature on the solution behavior of the copolymers were investigated comprehensively. Copolymer chains formed micelles at pH values higher than 5 whereas unimeric polymers were observed to exist below pH 5, owing to the repulsion between positively charged P4VP blocks. The size of the micelles was dependent on the relative length of blocks, P4VP and POEGMA. Thermo-responsive properties of copolymers were investigated depending on the pH and length of P4VP block. The increase in the length of P4VP block decreased the LCST substantially at pH 7. At pH 3, LCST of copolymers shifted to higher temperatures due to the increased interaction of copolymers with water through positively charged P4VP block.Article Citation - WoS: 20Citation - Scopus: 22A New Proton Sponge Polymer Synthesized by Raft Polymerization for Intracellular Delivery of Biotherapeutics(Royal Society of Chemistry, 2014) Kurtuluş, Işıl; Yılmaz, Gökhan; Üçüncü, Muhammed; Emrullahoğlu, Mustafa; Becer, C. Remzi; Bulmuş, VolgaA spermine-like polymer was synthesized via reversible addition- fragmentation chain transfer polymerization as a potential endosomal escaping agent. A new methacrylate monomer, 2-((tert-butoxycarbonyl)(2-((tert- butoxycarbonyl)amino)ethyl)amino)ethylmethacrylate (BocAEAEMA), was prepared and then polymerized via RAFT polymerization at constant monomer or initiator concentration at varying [M]/[R]/[I] ratios. In all polymerizations, ln[M] 0/[M] increased linearly with time. The linear increase in M n with monomer conversion was also observed. P(BocAEAEMA)s with controlled molecular weights and narrow molecular weight distributions were obtained. The in vitro cytotoxicity and proton sponge capacity of deprotected polymers P(AEAEMA) were investigated in comparison with a widely used endosomal-disruptive polymer, PEI. P(AEAEMA)s were found to possess proton sponge capacity comparable with PEI. More importantly, P(AEAEMA)s were not toxic on NIH 3T3 cells at concentrations where PEI (25 kDa) was highly toxic (0.4 μM and above). P(AEAEMA) was able to fully condense a DNA fragment at nitrogen/phosphate (N/P) ratios of 10 and above, as evidenced by gel electrophoresis. P(BocAEAEMA) was then chain-extended with a model sugar monomer, mannose-acrylate (ManAc), to yield P(AEAEMA)-b-P(ManAc) block copolymers, to potentially provide cell-recognition ability to the polyplex particles. Although the presence of the P(ManAc) block partially inhibited the interaction of P(AEAEMA) with DNA, P(AEAEMA)13-b-P(ManAc)7 was able to form polyplexes with DNA at N/P ratios ranging between 20/1 and 2/1. Dynamic light scattering measurements showed that while P(AEAEMA) (M n = 5.5 kDa) and DNA formed polyplex particles having a hydrodynamic diameter (Dh) of 125 ± 51 nm, P(AEAEMA)13-b- P(ManAc)7 and DNA formed particles with a smaller Dh of 38 ± 10 nm.Article Citation - WoS: 52Citation - Scopus: 53Raft Polymerization Mediated Bioconjugation Strategies(Royal Society of Chemistry, 2011) Bulmuş, VolgaThis review aims to highlight the use of RAFT polymerization in the synthesis of polymer bioconjugates. It covers two main bioconjugation strategies using the RAFT process: (i) post-polymerization bioconjugations using pre-synthesized reactive polymers, and (ii) bioconjugations via in situ polymerization using biomolecule-modified monomers or chain transfer agents. © 2011 The Royal Society of Chemistry.