Browsing by Author "Yildirim, Ozge Caglar"

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Boron Nitride Nanoparticles Loaded with a Boron-Based Hybrid as a Promising Drug Carrier System for Alzheimer's Disease Treatment
(MDPI, 2022) Yildirim, Ozge Caglar; Arslan, Mehmet Enes; Oner, Sena; Cacciatore, Ivana; Di Stefano, Antonio; Mardinoglu, Adil; Turkez, Hasan
The search for an innovative and effective drug delivery system that can carry and release targeted drugs with enhanced activity to treat Alzheimer's disease has received much attention in the last decade. In this study, we first designed a boron-based drug delivery system for effective treatment of AD by integrating the folic acid (FA) functional group into hexagonal boron nitride (hBN) nanoparticles (NPs) through an esterification reaction. The hBN-FA drug carrier system was assembled with a new drug candidate and a novel boron-based hybrid containing an antioxidant as BLA, to constitute a self-assembled AD nano transport system. We performed molecular characterization analyses by using UV-vis spectroscopy, Fourier transform infrared spectrophotometer (FTIR), scanning electron microscope (SEM), Energy-dispersive X-ray spectroscopy (EDS) and Zeta potential investigations. Second, we tested the anti-Alzheimer properties of the carrier system on a differentiated neuroblastoma (SHSY5-Y) cell line, which was exposed to beta-amyloid (1-42) peptides to stimulate an experimental in vitro AD model. Next, we performed cytotoxicity analyses of synthesized molecules on the human dermal fibroblast cell line (HDFa) and the experimental AD model. Cytotoxicity analyses showed that even higher concentrations of the carrier system did not enhance the toxicological outcome in HDFa cells. Drug loading analyses reported that uncoated hBN nano conjugate could not load the BLA, whereas the memantine loading capacity of hBN was 84.3%. On the other hand, memantine and the BLA loading capacity of the hBN-FA construct was found to be 95% and 97.5%, respectively. Finally, we investigated the neuroprotective properties of the nano carrier systems in the experimental AD model. According to the results, 25 mu g/mL concentrations of hBN-FA+memantine (94% cell viability) and hBN-FA+BLA (99% cell viability) showed ameliorative properties against beta-amyloid (1-42) peptide toxicity (50% cell viability). These results were generated through the use of flow cytometry, acetylcholinesterase (AChE) and antioxidant assays. In conclusion, the developed drug carrier system for AD treatment showed promising potential for further investigations and enlightened neuroprotective capabilities of boron molecules to treat AD and other neurodegenerative diseases. On the other hand, enzyme activity, systematic toxicity analyses, and animal studies should be performed to understand neuroprotective properties of the designed carrier system comprehensively.
Exploring the Potential of Anthracene Derivatives as Fluorescence Emitters for Biomedical Applications
(Royal Society of Chemistry, 2023) Aydemir, Murat; Haykir, Gulcin; Selvitopi, Harun; Yildirim, Ozge Caglar; Arslan, Mehmet Enes; Abay, Bahattin; Turksoy, Figen
Two novel anthracene derivatives were synthesized, and detailed photo-physical and biological investigations were carried out using a variety of spectroscopy techniques. The effect of cyano (-CN) substitution was found to be effective to alter the charge population and frontier orbital energy levels via Density Functional Theory (DFT) calculations. Particularly, the introduction of styryl and triphenylamine groups attached to the anthracene core helped to increase the conjugation relative to the anthracene moiety. The results revealed that the molecules have intramolecular charge transfer (ICT) properties, occurring from the electron donating triphenylamine to the electron accepting anthracene moiety in solutions. In addition, the photo-physical properties are strongly cyano-dependent, where the cyano-substituted (E/Z)-(2-anthracen-9-yl)-3-(4 '-(diphenylamino)biphenyl-4yl)acrylonitrile molecule showed stronger electron affinity due to the enhanced internal steric hindrance compared to the (E)-4 '-(2-(anthracen-9-yl)vinyl)-N,N-diphenylbiphenyl-4-amine molecule, which resulted in a lower photoluminescence quantum yield (PLQY) value and a shorter lifetime in the molecule. Besides, the Molecular Docking approach was used to investigate possible cellular staining targets to confirm cellular imaging potential of the compounds. Moreover, cell viability analyses put forth that synthesized molecules do not exhibit significant cytotoxicity under 125 mu g mL(-1) concentration on the human dermal fibroblast cell line (HDFa). Moreover, both of the compounds showed great potential in cellular imaging of HDFa cells. Compared to Hoechst 33258, a common fluorescent dye used for nuclear staining, the compounds showed higher magnification of cellular structure imaging capacity by staining the whole cellular compartment. On the other hand, bacterial staining showed that ethidium bromide has higher resolution in monitoring Staphylococcus aureus (S. aureus) cell culture.
Green Synthesis of Magnesium Oxide Nanoparticles by Using Petroselinum Crispum Extract and Their Potent Antibacterial and Wound Healing Properties
(Elsevier, 2025) Yildirim, Ozge Caglar; Turkez, Hasan
The popularity of plant-mediated green synthesis is increasing due to its simplicity, costeffectiveness, eco-friendliness and versatility. The synthesis of metal oxide nanoparticles based on plant extracts facilitates the production of non-toxic nanoparticles owing to the presence of several plant chemicals and biochemical compounds which are beneficial for biological and pharmaceutical applications. In the present study, leaf extracts of Petroselinum crispum were used for the synthesis of magnesium oxide (MgO) nanoparticles. The biophysical properties of the synthesized MgO nanoparticles were investigated using ultraviolet-visible spectroscopy. Furthermore, Fourier-transform infrared spectroscopy (FTIR) and scanning electron microscopy (SEM) were employed to determine and analyse the functional groups and morphology of the nanoparticles. The maximum peak was found at 210 nm using UV-visible spectroscopy. This finding is indicative of the formation of MgO nanoparticles within the sample. The FTIR results showed that the modifications in the functional groups are responsible for the formation of nanoparticles. The presence of magnesium oxide was confirmed by the peak at 652 cm-1. Furthermore, the SEM images revealed that the particle size of the samples was in the range of 50-100 nm. The investigation then turned to the assessment of the potential toxicity of the greensynthesized MgO nanoparticles in healthy human dermal fibroblasts. The study revealed that the particles were not toxic in the concentration range of 0-400 mu g/mL. Furthermore, the biosynthesised particles have the potential to promote cell proliferation in vitro wound model. In addition, the antimicrobial activity of the MgO nanoparticles against Escherichia coli and Streptococcus aureus bacteria was demonstrated.
In Vitro Transcriptome Analysis of Cobalt Boride Nanoparticles on Human Pulmonary Alveolar Cells
(MDPI, 2022) Arslan, Mehmet Enes; Tatar, Arzu; Yildirim, Ozge Caglar; Sahin, Irfan Oguz; Ozdemir, Ozlem; Sonmez, Erdal; Turkez, Hasan
Nanobiotechnology influences many different areas, including the medical, food, energy, clothing, and cosmetics industries. Considering the wide usage of nanomaterials, it is necessary to investigate the toxicity potentials of specific nanosized molecules. Boron-containing nanoparticles (NPs) are attracting much interest from scientists due to their unique physicochemical properties. However, there is limited information concerning the toxicity of boron-containing NPs, including cobalt boride (Co2B) NPs. Therefore, in this study, Co2B NPs were characterized using X-ray crystallography (XRD), transmission electron microscope (TEM), scanning electron microscope (SEM), and energy-dispersive X-ray spectroscopy (EDX) techniques. Then, we performed 3-(4,5-dimethyl-thiazol-2-yl) 2,5-diphenyltetrazolium bromide (MTT), lactate dehydrogenase (LDH) release, and neutral red (NR) assays for assessing cell viability against Co2B NP exposure on cultured human pulmonary alveolar epithelial cells (HPAEpiC). In addition, whole-genome microarray analysis was carried out to reveal the global gene expression differentiation of HPAEpiC cells after Co2B NP application. The cell viability tests unveiled an IC50 value for Co2B NPs of 310.353 mg/L. The results of our microarray analysis displayed 719 gene expression differentiations (FC >= 2) among the analyzed 40,000 genes. The performed visualization and integrated discovery (DAVID) analysis revealed that there were interactions between various gene pathways and administration of the NPs. Based on gene ontology biological processes analysis, we found that the P53 signaling pathway, cell cycle, and cancer-affecting genes were mostly affected by the Co2B NPs. In conclusion, we suggested that Co2B NPs would be a safe and effective nanomolecule for industrial applications, particularly for medical purposes.
Lipoic Acid Conjugated Boron Hybrids Enhance Wound Healing and Antimicrobial Processes
(MDPI, 2023) Turkez, Hasan; Yildirim, Ozge Caglar; Oner, Sena; Kadi, Abdurrahim; Mete, Abdulkadir; Arslan, Mehmet Enes; Mardinoglu, Adil
Complications of chronic non-healing wounds led to the emergence of nanotechnology-based therapies to enhance healing, facilitate tissue repair, and prevent wound-related complications like infections. Here, we design alpha lipoic acid (ALA) conjugated hexagonal boron nitride (hBN) and boron carbide (B4C) nanoparticles (NPs) to enhance wound healing in human dermal fibroblast (HDFa) cell culture and characterize its antimicrobial properties against Staphylococcus aureus (S. aureus, gram positive) and Escherichia coli (E. coli, gram negative) bacterial strains. ALA molecules are integrated onto hBN and C4B NPs through esterification procedure, and molecular characterizations are performed by using transmission electron microscopy (TEM), Fourier transform infrared spectroscopy (FTIR), and UV-vis spectroscopy. Wound healing and antimicrobial properties are investigated via the use of cell viability assays, scratch test, oxidative stress, and antimicrobial activity assays. Based on our analysis, we observe that ALA-conjugated hBN NPs have the highest wound-healing feature and antimicrobial activity compared to ALA-B4C. On the other hand, hBN, ALA-B4C, and ALA compounds showed promising regenerative and antimicrobial properties. Also, we find that ALA conjugation enhances wound healing and antimicrobial potency of hBN and B4C NPs. We conclude that the ALA-hBN conjugate is a potential candidate to stimulate regeneration process for injuries.
Neutralization of Iron Oxide Magnetic Nanoparticle Aquatoxicity on Oncorhynchus Mykiss Via Supplementation with Ulexite
(Taylor & Francis Ltd, 2024) Ucar, Arzu; Arslan, Mehmet Enes; Yeltekin, Asli Cilingir; Ozgeris, Fatma Betul; Yildirim, Ozge Caglar; Parlak, Veysel; Atamanalp, Muhammed
Nowadays, the unique features of nanoparticles (NPs) have encouraged new applications in different areas including biology, medicine, agriculture, and electronics. Their quick joining into daily life not only enhances the uses of NPs in a wide range of modern technologies but also their release into the aquatic environment causes inevitable environmental concerns. On the other hand boron exhibits key physiological effects on biological systems. This research was designed for evaluating the toxicity of magnetite nanoparticles (Fe3O4-MNPs) on aquatic organisms and obtaining data for the information gap in this area. In this study, Rainbow trout (Oncorhynchus mykiss) was considered as an aquatic indicator, and trials were designed as Ulexite (a boron mineral, UX) treatment against exposure to Fe3O4-MNPs. Synthesized and characterized Fe3O4-MNPs were exposed to rainbow trouts in wide spectrum concentrations (0.005-0.08 mL/L) to analyze its lethal dose (LC50) and cytoprotective properties by UX treatment were assessed against Fe3O4-MNPs applications for 96 h. For the initial toxicity analysis, hematological parameters (blood cell counts) were examined in experimental groups and micronucleus (MN) assay was performed to monitor nuclear abnormalities after exposure to NPs. Biochemical analyzes in both blood and liver samples were utilized to assess antioxidant/oxidative stress and inflammatory parameters. Also, 8-hydroxy-2'-deoxyguanosine (8-OHdG) assay was used to investigate oxidative DNA lesions and Caspase-3 analysis was performed on both blood and liver tissues to monitor apoptotic cell death occurrence. When antioxidant enzymes in blood and liver tissue were examined, time-dependent decreases in activity were determined in SOD, CAT, GPx, and GSH enzymes, while increased levels of MDA and MPO parameters were observed in respect to Fe3O4-MNPs exposure. It was found that TNF-alpha, Il-6 levels were enhanced against Fe3O4-MNPs treatment, but Nrf-2 levels were decreased at the 46th and 96th h. In the 96th application results, all parameters were statistically significant (p < 0.05) in blood and liver tissue, except for the IL-6 results. It was determined that the frequency of MN, the level of 8-OHdG and caspase-3 activity increased in respect to Fe3O4-MNPs exposure over time. Treatment with UX alleviated Fe3O4-MNPs-induced hematotoxic and hepatotoxic alterations as well as oxidative and genetic damages. Our findings offer strong evidence for the use of UX as promising, safe and natural protective agents against environmental toxicity of magnetite nanoparticles.
New Gene Targets for Diagnosis and Therapy of Diabetic Retinopathy
(Aves, 2025) Cinici, Emine; Arslan, Mehmet Enes; Yildirim, Ozge Caglar; Dilekmen, Nilay; Utlu, Bahadir; Cinici, Ozkan; Turkez, Hasan
Objective: Diabetic retinopathy (DR), considered one of the most common microvascular complications associated with diabetes mellitus (DM), involves both neuronal and vascular dysfunctions in the retina. Neuronal damage and vision loss occur progressively in patients with DR. A number of genetic targets have been identified for DR and gene-related treatments as well as early diagnostic techniques have been developed. Despite some medical advances, DR remains a devastating complication of diabetes. This study aimed to identify new gene targets that can be used for the prognosis and treatment of DR.. Materials and Methods: Eight candidate genes were analyzed using Synergy Brands Green (SYBR-green)- based real-time polymerase chain reaction in peripheral blood mononuclear cells (PBMCs) from 45 individuals: DR patients (n=15), DM patients without DR (n=15), and healthy controls (n=15). STRING v11 was used for protein-protein interaction analysis. Gene expression differences were evaluated using ANOVA, with significance set at P < .05. Results: HIF1A and VEGFA were significantly upregulated in both DR and DM groups compared to controls (HIF1A: fold change 5.28; VEGFA: fold change 5.20 for DR group). SERPING1 was specifically upregulated in DR patients (fold change 3.42). CX3CR1 and BDNF were downregulated in both DR and DM groups (CX3CR1: fold change 8.32; BDNF: fold change 3.21), while IGFBP3 was significantly downregulated only in DR patients (fold change 6.5). STRING analysis revealed strong interactions between SERPING1 and complement pathway components, while IGFBP3 was linked to insulin-like growth factor signaling. Conclusion: In light of these findings, we observed that SERPING1 and IGFBP3 genes might be proposed as targets for early diagnosis and treatment for DR.
Synthesis and Characterization of Memantine-Loaded Niosomes for Enhanced Alzheimer's Disease Targeting
(MDPI, 2025) Turkez, Hasan; Oner, Sena; Yildirim, Ozge Caglar; Arslan, Mehmet Enes; Dimmito, Marilisa Pia; Kahraman, cigdem Yuce; Mardinoglu, Adil
Background/Objectives: Over the past 25 years, numerous biological molecules, like recombinant lysosomal enzymes, neurotrophins, receptors, and therapeutic antibodies, have been tested in clinical trials for neurological diseases. However, achieving significant success in clinical applications has remained elusive. A primary challenge has been the inability of these molecules to traverse the blood-brain barrier (BBB). Recognizing this hurdle, our study aimed to utilize niosomes as delivery vehicles, leveraging the "molecular Trojan horse" technology, to enhance the transport of molecules across the BBB. Methods: Previously synthesized memantine derivatives (MP1-4) were encapsulated into niosomes for improved BBB permeability, hypothesizing that this approach could minimize peripheral drug toxicity while ensuring targeted brain delivery. Using the human neuroblastoma (SH-SY5Y) cell line differentiated into neuron-like structures with retinoic acid and then exposed to amyloid beta 1-42 peptide, we established an in vitro Alzheimer's disease (AD) model. In this model, the potential usability of MP1-4 was assessed through viability tests (MTT) and toxicological response analysis. The niosomes' particle size and morphological structures were characterized using scanning electron microscopy (SEM), with their loading and release capacities determined via UV spectroscopy. Crucially, the ability of the niosomes to cross the BBB and their potential anti-Alzheimer efficacy were analyzed in an in vitro transwell system with endothelial cells. Results: The niosomal formulations demonstrated effective drug encapsulation (encapsulation efficiency: 85.3% +/- 2.7%), controlled release (72 h release: 38.5% +/- 1.2%), and stable morphology (PDI: 0.22 +/- 0.03, zeta potential: -31.4 +/- 1.5 mV). Among the derivatives, MP1, MP2, and MP4 exhibited significant neuroprotective effects, enhancing cell viability by approximately 40% (p g/mL. The niosomal delivery system improved BBB permeability by 2.5-fold compared to free drug derivatives, as confirmed using an in vitro bEnd.3 cell model. Conclusions: Memantine-loaded niosomes provide a promising platform for overcoming BBB limitations and enhancing the therapeutic efficacy of Alzheimer's disease treatments. This study highlights the potential of nanotechnology-based delivery systems in developing targeted therapies for neurodegenerative diseases. Further in vivo studies are warranted to validate these findings and explore clinical applications.