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Browsing by Author "Ulu, Gizem Tugce"

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    Citation - WoS: 3
    Citation - Scopus: 3
    HER2-Specific Peptide (LTWWYSPY) and Antibody (Herceptin) Targeted Core Cross-Linked Micelles for Breast Cancer: A Comparative Study
    (MDPI, 2023) Bayram, Nazende Nur; Ulu, Gizem Tugce; Abdulhadi, Nusaibah Abdulsalam; Guerdap, Seda; Isoglu, Ismail Alper; Baran, Yusuf; Isoglu, Sevil Dincer; 01. Abdullah Gül University; 04. Yaşam ve Doğa Bilimleri Fakültesi; 04.01. Biyomühendislik
    This study aims to prepare a novel breast cancer-targeted micelle-based nanocarrier, which is stable in circulation, allowing intracellular drug release, and to investigate its cytotoxicity, apoptosis, and cytostatic effects, in vitro. The shell part of the micelle is composed of zwitterionic sulfobetaine ((N-3-sulfopropyl-N,N-dimethylamonium)ethyl methacrylate), while the core part is formed by another block, consisting of AEMA (2-aminoethyl methacrylamide), DEGMA (di(ethylene glycol) methyl ether methacrylate), and a vinyl-functionalized, acid-sensitive cross-linker. Following this, a targeting agent (peptide (LTVSPWY) and antibody (Herceptin((R)))), in varying amounts, were coupled to the micelles, and they were characterized by H-1 NMR, FTIR (Fourier-transform infrared spectroscopy), Zetasizer, BCA protein assay, and fluorescence spectrophotometer. The cytotoxic, cytostatic, apoptotic, and genotoxic effects of doxorubicin-loaded micelles were investigated on SKBR-3 (human epidermal growth factor receptor 2 (HER2)-positive) and MCF10-A (HER2-negative). According to the results, peptide-carrying micelles showed a higher targeting efficiency and better cytostatic, apoptotic, and genotoxic activities than antibody-carrying and non-targeted micelles. Also, micelles masked the toxicity of naked DOX on healthy cells. In conclusion, this nanocarrier system has great potential to be used in different drug-targeting strategies, by changing targeting agents and drugs.
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    Citation - WoS: 12
    Citation - Scopus: 12
    HER2-Targeted, Degradable Core Cross-Linked Micelles for Specific and Dual pH-Sensitive Dox Release
    (Wiley-VCH Verlag GmbH, 2022) Bayram, Nazende Nur; Ulu, Gizem Tugce; Topuzogullari, Murat; Baran, Yusuf; Isoglu, Sevil Dincer; 01. Abdullah Gül University; 04. Yaşam ve Doğa Bilimleri Fakültesi; 04.01. Biyomühendislik
    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.
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    Peptide Targeted Core Cross-Linked Micelles for Dox Delivery to HER2 Expressing Cancer Cells
    (Mary Ann Liebert, inc, 2022) Bayram, Nazende Nur; Ulu, Gizem Tugce; Gurdap, Seda; Isoglu, Ismail Alper; Baran, Yusuf; Isoglu, Sevil Dincer; 01. Abdullah Gül University; 04. Yaşam ve Doğa Bilimleri Fakültesi; 04.01. Biyomühendislik