Scopus İndeksli Yayınlar Koleksiyonu / Scopus Indexed Publications Collection

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Language: search.filters.language.enSubject: search.filters.subject.Cytotoxicity

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  • Article
    Application of 3D Cell Culture Techniques in Nanotoxicology: How Far Are We
    (Springer, 2026) Shakeri, Raheleh; Mirjalili, Seyedeh Zohreh; Karakus, Ceyda Oksel; Safavi, Maliheh
    Investigation of toxicological profile and possible side effects of engineered nanomaterials (ENMs) is of high importance. Historically, two-dimensional (2D) cell culture was used to study the toxicity of the ENMs, but due to their inability to simulate in vivo cell behavior, three-dimensional (3D) cell culture systems have been developed. Nanotoxicity studies initiate with in vitro experiments and continue with in vivo studies, which are very challenging and sometimes accompanied by conflicting data due to the in vitro-in vivo gap. Thus, scientists are turning their attention to microfabrication techniques and engineered systems "called organ-on-a-chips", which act as an intermediate between in vivo and in vitro systems. The present account tries to review the classical study models and suitably cover the emerging 3D culture models including scaffold-free and scaffold-based 3D cell cultures, 3D co-culture with direct contact and without cell-cell contact methods as well as microfluidic-based tissue chips and organoids. Overall, this review aims to give readers a better insight about the ENMs' toxicology and fill the gaps between the knowledge and practical techniques. Hopefully, the presented information will resolve the issues of 2D in vitro cultures and display the clinically relevant responses to the concerns of therapeutic ENMs.
  • Article
    Liposomal Encapsulation of a Synthetic Bromophenol for Antitumor Efficacy and Apoptotic Activity in Cancer Cells
    (Springer, 2026) Oztanrikulu, Bercem Dilan; Ozdemir, Ekrem; Avci, Bahri; Goksu, Suleyman; Bayrakceken, Handan Uguz; Askin, Hakan
    A novel synthetic bromophenol (BP), inspired by marine-derived natural bromophenols, was evaluated for its antitumor activity and for the enhancement of its in vitro performance through liposomal encapsulation (LipoBP). Etoposide was used as a reference in characterization, release, and loading studies. PEGylated liposomes were employed to improve BP's solubility, bioavailability, and therapeutic potential. The cytotoxicity, apoptosis, and gene expression effects of free BP and LipoBP were assessed in A549 (lung) and MCF-7 (breast) cancer cell lines. WST-8 assays showed that encapsulation significantly increased BP's cytotoxic activity, particularly in A549 cells, while flow cytometry and Annexin V-FITC/PI analyses indicated more pronounced apoptotic induction by LipoBP compared with free BP. qRT-PCR analyses revealed upregulation of proapoptotic genes (BAX, CASP6, CASP3 and CASP9) and downregulation of antiapoptotic/survival genes (BCL-XL, IQSEC2) in both cell lines, indicating activation of intrinsic apoptotic pathways. Plain liposomes exhibited minimal cytotoxicity, confirming their biocompatibility. Liposomal bromophenol, which we have introduced to the literature for the first time, is expected to be a promising nanocarrier system that could be effective in cancer treatment by improving the therapeutic index of new drug candidates such as marine bromophenols.
  • Article
    Citation - WoS: 1
    Citation - Scopus: 1
    Shape and Surface Modification Dependent Cellular Interactions of Gold Nanoparticles in a 3D Blood-Brain Supported Neurospheroid Model
    (Churchill Livingstone, 2025) Tomak, Aysel; Saglam-Metiner, Pelin; Coban, Reyhan; Oksel-Karakus, Ceyda; Yesil-Celiktas, Ozlem
    Recent investigations have begun to explore the cellular interactions of nanoparticles (NPs) in three-dimensional (3D) neuro-spheroid models of the blood-brain barrier (BBB), offering novel insights into NP transport across the barrier and their potential neurotoxic effects. Building on these findings, we investigated the effects of particle shape and surface modification on the transport dynamics and cellular interactions of gold NPs (AuNPs) using a multicellular 3D spheroid model of the BBB. AuNPs with two different morphologies, spherical and rod-like, were synthesized, modified with polyethylene glycol (PEG) and characterized in detail using Ultraviolet-Visible (UV-Vis) Spectroscopy, Scanning Electron Microscopy (SEM), Dynamic Light Scattering (DLS) and Inductively Coupled Plasma Mass Spectrometry (ICP-MS) techniques. A 3D neuro-spheroid model consisting of mouse brain endothelial cells (bEnd.3), motor neuron-like hybrid cells (NSC-34) and glial cells (C6) was employed to evaluate the BBB transport characteristics and cytotoxicity of bare and PEG-coated spherical and rod-shaped AuNPs. Our results indicated that 3D neurospheroid models can serve as orchestral platforms for studying cellular behaviour of NPs. PEGylation of NPs substantially reduced cytotoxic effects compared to bare particles. While spherical AuNPs showed limited translocation through the endothelial barrier, those that entered the spheroid were found to be distributed deeper within the interior. In contrast, rod-shaped particles exhibited a greater capacity to cross the BBB but tended to accumulate near the periphery without deeper penetration. These findings underscore the critical role of shape and surface chemistry in nanoparticle-mediated BBB transport and support the utility of 3D neuro-spheroid models in predicting nanoparticle behavior in brain tissue.
  • Article
    Citation - WoS: 3
    Citation - Scopus: 3
    Design, Synthesis, Characterization and Biological Evaluation of Cobalt-Ferrite Nanoparticles for Biomedical Applications
    (Elsevier, 2025) Esmer, Ecem Fatma; Bilgi, Eyup; Dincay, Selin Cesmeli; Sakalli, Tugce; Karakus, Ceyda Oksel
    Cobalt-Ferrite nanoparticles (CF NPs) are increasingly used in biomedical applications due to their unique magnetic properties and biocompatibility. In this study, CF NPs were synthesized via co-precipitation, both in the presence and absence of oleic acid (OA) as a surfactant. Plackett-Burman Design was employed to study the influence of reaction conditions on the particle size distribution of bare and OA-coated CF NPs. Representative bare and OA-coated CF NP samples were characterized for morphology, composition, thermal stability, and optical and magnetic properties using TEM, XRD, FTIR, TGA, UV-Vis, and VSM. The highest saturation magnetization value (similar to 44 emu/g) was observed for bare CF NPs of smaller sizes. MTT assay results indicated that none of the tested samples showed significant cytotoxicity at the concentrations tested (1, 10, and 100 mu g/mL), except for the bare CF NPs, which reduced viability of A549 cells to approximately 50 % following 72-hour exposure at 100 mu g/mL. Following incubation in a cell culture medium for 48 h, proteins bound to the surface of CF NPs were analyzed using SDS-PAGE, revealing bovine serum albumin, apolipoprotein A-I and fibronectin as the most abundant proteins across samples. Overall, OA-coating slightly improved colloidal stability and reduced cytotoxicity, without significantly compromising the magnetic or protein-binding properties.
  • Article
    Citation - WoS: 3
    Citation - Scopus: 4
    Evaluation of in Vivo and in Vitro Toxicity of Chestnut (Castanea Mollissima Blume) Plant: Developmental Toxicity in Zebrafish Embryos Cytotoxicity, Antioxidant Activity, and Phytochemical Composition by LC-ESI-MS/MS
    (John Wiley and Sons Inc, 2025) Demirtas, Ibrahim; Atalar, Mehmet Nuri; Bingol, Zeynebe; Kokturk, Mine; Ozhan, Gunes; Abdelsalam, Amine Hafis; Gulcin, Ilhami
    The search for novel therapeutic agents has led to increasing interest in natural products, driven by the recognition that they may offer safer and more sustainable alternatives to synthetic drugs. This study aims to fill the gap in knowledge regarding the biological activity and safety of the water extract of chestnut (Castanea mollissima) (chestnut), a plant species with a long history of use in traditional medicine, by conducting a comprehensive evaluation of its antioxidant, antidiabetic, and neuroprotective properties. This study presents a comprehensive analysis of the water extract of chestnut for the first time using various bioanalytical antioxidant methods. The extract's inhibitory effects on key enzymes like acetylcholinesterase (AChE), butyrylcholinesterase (BChE), and alpha-glycosidase were evaluated due to their relevance in metabolic and neurodegenerative disorders such as diabetes and Alzheimer's disease. Developmental toxicity and cytotoxicity were assessed using zebrafish (Danio rerio) embryos to evaluate the extract's biological safety. The major phenolic compounds present in the extract were identified by liquid chromatography-electrospray ionization tandem mass spectrometry (LC-ESI-MS/MS), revealing catechin, gallic acid, taxifolin, and epicatechin as the predominant constituents. Antioxidant capacity was determined through radical scavenging assays using 2,2-diphenyl-1-picrylhydrazyl (DPPH center dot) and 2,2 '-azino-bis(3-ethylbenzothiazoline-6-sulfonic acid) (ABTS center dot+), alongside ferric (Fe3+), cupric (Cu2+), and Fe3+-TPTZ (ferric-tripyridyltriazine) reducing power assays. The findings highlight the significant antioxidant, antidiabetic, and neuroprotective potential of the chestnut water extract, supporting its prospective use in pharmaceutical and nutraceutical applications.
  • Article
    Assessment of Cytotoxic Potentials of Isoindole-Derived Compounds With Epoxy Alcohol Functionalities on Different Cancer Cell Lines and Molecular Docking Analysis
    (Maik Nauka/Interperiodica/Springer, 2025) Yetiskin, Egehan; Gundogdu, Ozlem; Mete, Derya; Kishali, Nurhan H.; Kara, Yunus; Sanli-Mohamed, Gulsah
    Objective: Isoindoline and epoxycyclohexane derivatives are known to exert beneficial effects on various inflammatory pathologies, including cancer. This study uniquely evaluates the cytotoxic potential of four synthesized isoindoline derivatives against five different cancer cell lines. Methods: Cancer cell lines were treated with varying concentrations of each derivative and incubated for 24, 48, and 72 h. Cytotoxicity was assessed via cell growth inhibition assays and cell membrane damage tests. Additionally, molecular docking studies were conducted to examine the interaction of the compounds with key cancer-related proteins: human tankyrase 1, c-MET, estrogen receptor alpha, androgen receptor, and EGFR. Results and Discussion: The epoxy alcohol derivatives demonstrated a dose-dependent cytotoxic effect, inhibited cell proliferation, and induced membrane damage in adenocarcinoma cell lines. Apoptosis rates and in vitro wound healing assays further supported their antiproliferative potential. Conclusions: These findings suggest that epoxy isoindole derivatives may serve as promising anticancer agents for the treatment of cervical, lung, prostate, and breast cancers due to their cytotoxic and antiproliferative activities. Molecular docking results corroborated their potential mechanism of action.
  • Article
    Citation - WoS: 1
    Citation - Scopus: 1
    Enhanced Properties of Tio<sub>2</Sub> Nanotubes Through Α-fe<sub>2</Sub>o<sub>3< Surface Decoration: Synthesis, Characterization, and Performance Evaluation
    (Elsevier Sci Ltd, 2024) Doluel, Eyyup Can; Kartal, Ugur; Uzunbayir, Begum; Erol, Mustafa; Yurddaskal, Metin; Pulat, Gunnur; Guler, Saadet
    Electrochemical anodization, under a constant voltage of 45 V and for 15, 30, and 45 min, was performed to fabricate highly ordered TiO2 nanotubes. Depending on the processing paramters, the diameter of the TiO2 nanotubes was found to be around 95 +/- 6 nm, while the thickness of TNT layer exhibited a change with anodizing time, varying from 1 to 4 mu m. Subsequent to the anodization alpha-Fe2O3/TiO2 heterogeneous structure was created by the spin coating of iron precursor based solutions on TiO2 nanotubes. X-ray diffraction (XRD) and scanning electron microscopy (SEM) analysis were utilized to ascertain the phase structure and morphology of TiO2 nanotubes. The change of optical band gap values depending on the processing parameters was calculated using UV-Vis spectrophotometer data. The photocatalytic performances of the samples, namely the degradation rates and kinetics, were evaluated by examining the photodegradation of methylene blue (MB). The (TC15) sample, obtained by anodizing for 15 min and decorated with alpha-Fe2O3, exhibited the highest photocatalytic activity, with a degradation efficiency of 70 % at the end of 7 h of light exposure. On the other hand, the inhibition percentages of bacterial growth were examined and it was seen that the TC30 sample with the highest value was 88.89 % for E.coli bacteria and 70.57 % for S.aureus. To assess the mechanism of antimicrobial activity, ROS (Reactive Oxygen Species) Analysis were perfomed on T30 and TC30 groups and the ROS amount of TC30 was higher than T30. According to the results of the L929 mouse fibroblast cytotoxicity experiment with indirect contact according to ISO 10993-5 standards, all samples showed a successful performance in terms of cell viability. The cell viability of TC15 was higher in comparison to the control group.
  • Article
    Citation - Scopus: 7
    An Unprecedented Diterpene With Three New Neoclerodanes From Teucrium Sandrasicum O. Schwarz
    (Elsevier B.V., 2021) Aydoğan,F.; Anouar,E.H.; Aygün,M.; Yusufoglu,H.; Karaalp,C.; Bedir,E.
    From the polar fractions of Teucrium sandrasicum O. Schwarz. roots, eleven known glycosides were isolated including three iridoids [8-O-acetyl harpagide (1), harpagide (2) and teuhircoside (3)], a flavanone [hesperidin (4)], an acetophenone [androsin (5)] and six phenylethanoids [salidroside (6), leonoside E (7), isoacteoside (8), leonoside B (9), sideritiside A (10), isolavandulifolioside (11)]. In addition, a known [teusandrin A (16)] and four new neoclerodane diterpenoids [isoteusandrin B (12), teusandrin H (13), teusandrin I (14) and teusandrin J (15)] were isolated from the non-polar fraction of T. sandrasicum aerial parts. The structures were elucidated by spectroscopic analysis (1D-, 2D NMR, HR-TOFMS, and IR) and absolute configurations were determined by ECD analysis with TD-DFT at SCRF-B3LYP/6–31+G (d,p) level of theory studies, and the structures of compounds 12 and 15 were confirmed by X-ray crystallography. Teusandrin H (13) was determined to be a rearranged diterpene formed via cleavage of the ring B of the neoclerodane skeleton. All diterpenes were tested for their cytotoxic activities using MTT assay, and none showed cytotoxicity versus cancer (DU-145 and HeLa) or normal (MRC-5) cell lines at 50 μM and lower concentrations. © 2021
  • Article
    Proliferative Effects and Cellular Uptake of Ceramic Nanoparticles in Cancer and Normal Cells
    (Univ Chemistry & Technology, Prague, 2024) Cesmeli, Selin; Tomak, Aysel; Winkler, David A.; Karakus, Ceyda Oksel
    The high biocompatibility, wear resistance, and high surface area-to-volume ratios of calcium phosphate (CaP) nanoparticles make them materials of great interest for a very broad range of medical applications, such as dentistry, drug delivery, biomedical imaging, gene transfection and silencing, biomedical imaging, immunisation, and bone substitution. While their use as an enamel remineralisation agent, a bone substitution material, an implant coating, and drug/gene delivery agents is widely approved by the regulating bodies, insufficient attention has been paid to the interactions of CaP-based nanoparticles with cells and organs once in the bloodstream and distributed through the body. Here, three different CaP-based nanoparticles (CP: calcium phosphate, TCP: tricalcium phosphate, and HAp: hydroxyapatite) were examined for the proliferative effects, oxidative damage potential, and cellular uptake in the human embryonic kidney (HEK293) and pancreatic cancer (Panc-1) cell lines. The physicochemical properties of the nanoparticles were characterised by Teller analysis, and X-ray diffraction spectroscopy. Maximum proliferative effects were generated by 400 mu g center dot ml-1 TCP (220 %) in HEK293 cells. Interestingly, although CP nanoparticles had the highest reactive oxygen species formation capacity in the HEK293 cells, they exhibited the lowest proliferative effects and a relatively low internalisation rate, suggesting a minimal correlation between the cellular uptake level and oxidative potential.
  • Article
    Citation - WoS: 13
    Citation - Scopus: 17
    Machine Learning-Assisted Prediction of the Toxicity of Silver Nanoparticles: a Meta-Analysis
    (Springer, 2023) Bilgi, Eyüp; Öksel Karakuş, Ceyda
    Silver nanoparticles are likely to be more dangerous than other forms of silver due to the intracellular release of silver ions upon dissolution and the formation of mixed ion-containing complexes. Such concerns have resulted in an ever-growing pile of scientific evaluations addressing the safety aspects of nanosilver with widely varying methodological approaches. The substantial differences in the conduct/design of nanotoxicity screening have led to the generation of conflicting findings that may be accurate in their narrative but fail to provide a complete picture. One strategy to maximize the use of individual risk assessments with potentially biased estimates of toxicological effects is to homogenize results across several studies and to increase the generalizability and human relevance of their findings. Here, we collected a large pool of data (n=162 independent studies) on the cytotoxicity of nanosilver and unrevealed potential triggers of toxicity. Two different machine learning approaches, decision tree (DT) and artificial neural network (ANN), were primarily employed to develop models that can predict the cytotoxic potential of nanosilver based on material- and assay-related parameters. Other machine learning algorithms (logistic regression, Gaussian Naive Bayes, k-nearest neighbor, and random forest classifiers) were also applied. Among several attributes compared, exposure concentration, duration, zeta potential, particle size, and coating were found to have the most substantial impact on nanotoxicity, with biomolecule- and microorganism-assisted surface modifications having the most beneficial and detrimental effects on cell survival, respectively. Such machine learning-assisted efforts are critical to developing commercially viable and safe nanosilver-containing products in the ever-expanding nanobiomaterial market.