Scopus İndeksli Yayınlar Koleksiyonu / Scopus Indexed Publications Collection
Permanent URI for this collectionhttps://hdl.handle.net/11147/7148
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Article Citation - WoS: 6Citation - Scopus: 6A Novel 2-Aminophenalenone Fluorescent Probe Designed for Monitoring H2o2 for in Vitro and in Vivo Bioimaging(Elsevier, 2024) Saygılı, Ecem; Ersöz Gülseven, Esra; Kıbrıs, Erman; Çakan Akdoğan, Gülçin; Üçüncü, MuhammedA significant compound in living organisms, hydrogen peroxide (H2O2) plays a dual role as a signalling molecule in cellular communication and as a pivotal biomarker in assessing disease and oxidative stress. Thus, the detection of abnormal changes in H2O2 levels is essential to understanding its function and involvement in biological systems. The growing demand to meet the specific needs for applications, particularly in biological systems, has sharpened focus on highly sensitive, highly selective molecular sensors and, in turn, heightened interest in these diagnostic tools with innovative designs. In our study, 2-aminophenalenone (2-AP) was used for the first time as a fluorophore in a fluorescent probe. The 2-APB molecule obtained from the reaction of 2-AP with 4-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl) benzyl chloroformate exhibited a highly selective and sensitive (i.e. 62 nM) detection profile for H2O2 compared with the other reactive oxygen species, anions, and metal cations. Moreover, offering naked-eye detection in aqueous solutions, 2-APB demonstrated excellent sensing performance, detection and real-time monitoring in relation to exogenous H2O2 in cells and endogenous H2O2 in zebrafish embryos. © 2024 Elsevier B.V.Article Citation - WoS: 13Citation - Scopus: 14Synthesis of Albumin Nanoparticles in a Water-Miscible Ionic Liquid System, and Their Applications for Chlorambucil Delivery To Cancer Cells(Elsevier, 2022) Akdoğan, Yaşar; Sözer, Sümeyra Çiğdem; Akyol, Cansu; Başol, Merve; Karakoyun, Çiğdem; Çakan Akdoğan, GülçinSerum albumin has been a preferred protein to generate biodegradable and non-toxic nanoparticles (NPs) for drug delivery applications. Different methods applied for the preparation of serum albumin NPs mostly used organic solvents. Here, we prepared serum albumin NPs in an ionic liquid (IL) system. ILs are considered to be green and designer solvents with unique properties that can replace organic solvents in the synthesis of albumin NPs. Bovine serum albumin (BSA) proteins dissolved in water were transformed into BSA NPs in a water/ Triton™X (TX-100), 1-butanol/1-butyl-3-methylimidazolium trifluoromethanesulfonate (BmimCF3SO3) microemulsion-like system by using a high-speed homogenizer and crosslinker glutaraldehyde. The obtained BSA NPs have been used in drug loading and release studies with a hydrophobic anticancer drug chlorambucil (Chl). Drug loading increased as increasing the ratio of Chl incubated with BSA NPs. Monitoring the drug release by UV–Vis spectroscopy revealed a burst release at first 4 h, but two-thirds of drugs stayed with NPs upon diffusion method. On the other hand, cellular uptake of Chl loaded BSA NPs caused a significant MCF7 breast cancer cell death, whereas free Chl and unloaded BSA NPs did not have a significant effect on the cell viability. Furthermore, in vivo toxicity assessment of BSA NPs obtained in the IL system was conducted in the zebrafish animal model. It showed that zebrafish body is able to eliminate BSA NPs without any toxic side effects and encapsulation of Chl into NPs reduced the toxicity of free Chl. In summary, we showed that BSA NPs with size smaller than 200 nm could be prepared in BmimCF3SO3 mediated system. They can be used for Chl loading (up to 6.9 wt%) with a sustainable release and they induce significant cell death in Chl sensitive cancer cells up to 45% in 24 h. These results indicate that BSA NPs could be prepared alternatively in IL systems and used in drug delivery studies.Article Citation - WoS: 10Citation - Scopus: 10An in Vivo Zebrafish Model Reveals Circulating Tumor Cell Targeting Capacity of Serum Albumin Nanoparticles(Elsevier, 2022) Çakan Akdoğan, Gülçin; Ersöz, Esra; Sözer, Sümeyra Çiğdem; Gelinci, EmineNanoparticles are promising tools of drug delivery in modern medicine. There is a need for fast and reliable models for in vivo validation of newly developed nanocarriers. Here, we report a fast and easy zebrafish larval model to study the biodistribution and cancer cell targeting capacity of serum albumin nanoparticles in vivo. Fluorescently tagged Bovine Serum Albumin Nanoparticles (BSA-NPs) delivered intravenously to the zebrafish larvae, can be used to study the biodistribution via live imaging. We showed that the BSA-NPs were instantly distributed to the larval vasculature including the brain, without causing any toxicity. The clearance of nanoparticles from the body occurred within few days, which gives sufficient time to study anti-cancer efficiency of the BSA-NPs. Next, we asked whether the BSA-NPs can target the cancer cells in circulation. We established a circulating tumor cell (CTC) xenograft model and described a quantitative method for colocalization and cancer cell death analysis in the intact live organism. We showed that BSA-NPs effectively found and localized to MCF7 cells in vasculature which were killed upon doxorubicin delivery. Interestingly, folic acid coating of BSA-NPs caused faster colocalization but did not increase the overall cell death. This is the first report of the biodistribution, toxicity and anti-cancer effectiveness of serum albumin-based nanoparticles in the zebrafish model. Moreover, here we report for the first time that BSA-NPs are able to target the CTCs in an in vivo model. The zebrafish CTC model and the analysis protocol reported here can be used to assess CTC targeting capacity of nanoparticles and devise patient specific CTC targeting tests.Article Citation - WoS: 7Citation - Scopus: 8Transcriptomics Profiling Identifies Cisplatin-Inducible Death Receptor 5 Antisense Long Non-Coding Rna as a Modulator of Proliferation and Metastasis in Hela Cells(Frontiers Media S.A., 2021) Gürer, Dilek Cansu; Erdoğan, İpek; Ahmadov, Ulvi; Başol, Merve; Sweef, Osama; Çakan Akdoğan, Gülçin; Akgül, BünyaminCisplatin is a well-known cancer chemotherapeutic agent but how extensively long non-coding RNA (lncRNA) expression is modulated by cisplatin is unknown. It is imperative to employ a comprehensive approach to obtain a better account of cisplatin-mediated changes in the expression of lncRNAs. In this study, we used a transcriptomics approach to profile lncRNAs in cisplatin-treated HeLa cells, which resulted in identification of 10,214 differentially expressed lncRNAs, of which 2,500 were antisense lncRNAs. For functional analyses, we knocked down one of the cisplatin inducible lncRNAs, death receptor 5 antisense (DR5-AS) lncRNA, which resulted in a morphological change in HeLa cell shape without inducing any cell death. A second round of transcriptomics-based profiling revealed differential expression of genes associated with immune system, motility and cell cycle in DR5-AS knockdown HeLa cells. Cellular analyses showed that DR5-AS reduced cell proliferation and caused a cell cycle arrest at S and G2/M phases. Moreover, DR5-AS knockdown reduced the invasive capacity of HeLa cells in zebrafish xenograft model. These results suggest that cisplatin-mediated pleiotropic effects, such as reduction in cell proliferation, metastasis and cell cycle arrest, may be mediated by lncRNAs. © Copyright © 2021 Gurer, Erdogan, Ahmadov, Basol, Sweef, Cakan-Akdogan and Akgül.Article Citation - WoS: 18Citation - Scopus: 20A Simple Desolvation Method for Production of Cationic Albumin Nanoparticles With Improved Drug Loading and Cell Uptake(Editions de Sante, 2020) Sözer, Sümeyra Çiğdem; Özmen Egesoy, Tuğçe; Başol, Merve; Çakan Akdoğan, Gülçin; Akdoğan, YaşarThe transport protein albumin has been used as a drug nanocarrier for a long time due to its versatility. Albumin is negatively charged at physiological conditions limiting its anionic drug loading capacity. However, loading of anionic drugs in the albumin nanoparticles (NPs), can be facilitated by albumin cationization. Here, we postulate a simple desolvation method for preparation of cationic albumin NPs with improved anionic drug loading. First, bovine serum albumin was cationized with ethylenediamine. Next, salicylic acid (SA) was added to the cationic bovine serum albumin (cBSA) solution prior to the desolvation. Among different desolvating agents tested, acetonitrile allowed the highest nanoparticle formation yield. The SEM analyses showed that the average size of cBSA NPs decreased from ~200 nm to ~100 nm upon SA loading. Moreover, the drug loading capacity of cBSA NPs was found to increase ~2 fold, and drug release was slower compared to BSA NPs. Finally, a significant increase in cellular uptake of cBSA NPs compared to that of native BSA NPs showed the potential for improved drug delivery. © 2020 Elsevier B.V.Article Citation - WoS: 33Citation - Scopus: 40Preparation of Albumin Nanoparticles in Water-In Liquid Microemulsions(Elsevier Ltd., 2019) Demirkurt, Begüm; Çakan Akdoğan, Gülçin; Akdoğan, YaşarIonic liquids (Its) with a variety of properties have been considered a unique class of solvents. Using ILs in microemulsions as oil substitutes provides environmentally benign media for various applications including nanoparticle synthesis. Here, bovine serum albumin nanoparticles (BSA NPs) widely used in drug delivery studies were prepared in nano-sized water droplets of water-in-IL (W/IL) microemulsion systems. A hydrophobic IL of 1-butyl-3-methylimidazolium hexafluorophosphate (BmimPF(6)) was used as oil component in place of oils (castor oil, olive oil, etc.) and/or conventional organic solvents (cyclohexane, dichloromethane, etc.) in an emulsification method. In order to obtain spherical BSA NPs, high speed homogenizer treatment was applied followed by glutaraldehyde addition. Effects of glutaraldehyde, speed of homogenizer, type of surfactants and compositional fractions of the microemulsion components on the formation of water droplets and/or preparation of BSA NPs were studied using FTIR, EPR, DLS, and SEM techniques. Optimization of these preparation parameters showed that 3 wt% of BSA in a water/Tween 20/BmimPF(6) microemulsion with 20:50:30 wt% yielded similar to 100 nm average sized BSA NPs based on the SEM analysis. Although, water droplet size strongly depends on the water content, BSA nanoparticle size did not show a significant dependency on the water content. On the other hand, surfactant/IL weight ratio is more crucial for obtaining more uniformly size distributed albumin nanoparticles. A significant cellular uptake of BSA NPs prepared in IL based microemulsions with high cell viability showed the potential of this technique in preparation of albumin nanoparticles that can be used also in drug delivery studies. (C) 2019 Elsevier B.V. All rights reserved.Article Citation - WoS: 22Citation - Scopus: 23A Guanidinium Modified Rhodamine-Based Fluorescent Probe for in Vitro/Vivo Imaging of Gold Ions(Royal Society of Chemistry, 2015) Karakuş, Erman; Çakan Akdoğan, Gülçin; Emrullahoğlu, MustafaWe devised a rhodamine-based fluorescent probe functionalized with a guanidinium moiety, which both operates efficiently in pure aqueous media and displays a selective fluorescence response to Au3+ ions. We also demonstrated the successful fluorescence imaging of Au3+ within living cells and a vertebrate species, the zebrafish.Article Citation - WoS: 33Citation - Scopus: 36Epr Studies of Intermolecular Interactions and Competitive Binding of Drugs in a Drug-Bsa Binding Model(Royal Society of Chemistry, 2016) Akdoğan, Yaşar; Emrullahoğlu, Mustafa; Tatlıdil, Diğdem; Üçüncü, Muhammed; Çakan Akdoğan, GülçinUnderstanding intermolecular interactions between drugs and proteins is very important in drug delivery studies. Here, we studied different binding interactions between salicylic acid and bovine serum albumin (BSA) using electron paramagnetic resonance (EPR) spectroscopy. Salicylic acid was labeled with a stable radical (spin label) in order to monitor its mobilized (free) or immobilized (bound to BSA) states. In addition to spin labeled salicylic acid (SL-salicylic acid), its derivatives including SL-benzoic acid, SL-phenol, SL-benzene, SL-cyclohexane and SL-hexane were synthesized to reveal the effects of various drug binding interactions. EPR results of these SL-molecules showed that hydrophobic interaction is the main driving force. Whereas each of the two functional groups (-COOH and -OH) on the benzene ring has a minute but detectable effect on the drug-protein complex formation. In order to investigate the effect of electrostatic interaction on drug binding, cationic BSA (cBSA) was synthesized, altering the negative net charge of BSA to positive. The salicylic acid loading capacity of cBSA is significantly higher compared to that of BSA, indicating the importance of electrostatic interaction in drug binding. Moreover, the competitive binding properties of salicylic acid, ibuprofen and aspirin to BSA were studied. The combined EPR results of SL-salicylic acid/ibuprofen and SL-ibuprofen/salicylic acid showed that ibuprofen is able to replace up to ∼83% of bound SL-salicylic acid, and salicylic acid can replace only ∼14% of the bound SL-ibuprofen. This indicates that ∼97% of all salicylic acid and ibuprofen binding sites are shared. On the other hand, aspirin replaces only ∼23% of bound SL-salicylic acid, and salicylic acid replaces ∼50% of bound SL-aspirin, indicating that ∼73% of all salicylic acid and aspirin binding sites are shared. These results show that EPR spectroscopy in combination with the spin labeling technique is a very powerful method to investigate drug binding dynamics in detail.