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Öğe Cytotoxicity and genotoxicity evaluations of oleic acid and conjugated linoleic acid(Istanbul Univ, Fac Pharmacy, 2022) Kizilsahin, Sadi; Karayildirim, Cinel Koksal; Bakan, Buket; Nalbantsoy, Ayse; Yavasoglu, Nefise KarabayBackground and Aims: Oleic acid (OLA) and conjugated linoleic acid (CLA) occur in dairy products and meats and are also widespread at lower levels in many other foodstuffs. It is known that OLA and CLA are very bioactive compounds with substantially anti-carcinogenic effects. The objective of this study was to evaluate the cytotoxic potentials of OLA and CLA which were tested against cancerous and non-cancerous cell lines and to determine their genotoxicity. Methods: The cytotoxic activities of OLA and CLA against to cancer cell lines (U-87-MG, A549, MCF-7, CaCo-2, HeLa and PC-3) and a control cell line (HEK293) were assessed by MIT assay. Ames MPFtm mutagenicity assay on 4 strains (TA98, TA100, TA 1535 and TA 1537) of Salmonella typhimurium was used for genotoxicity determination. Results: CLA showed cytotoxic activity on PC-3 cells, while OLA was created on A549 and PC-3 cell lines with the IC50 of 20 nM and 15 nM, respectively. No cytotoxic activity was observed on MCF-7, HeLa, U-87-MG, and CaCo-2 cells with the administered doses of OLA and CLA. It has been proved that OLA and CLA are characterized by a high cytotoxic activity towards cancer cells, as observed in the cell line test. There was no evidence for a mutagenic effect of OLA and CLA in the Ames test, with or without metabolic activation (S9) against Salmonella typhimurium strains. Conclusion: These in vitro test results indicate that these fatty acids can be considered a beneficial dietary supplement for enhancing anti-cancer therapy.Öğe Deciphering the biochemical similarities and differences among mouse embryonic stem cells, somatic and cancer cells using ATR-FTIR spectroscopy(Royal Soc Chemistry, 2018) Guler, Gunnur; Acikgoz, Eda; Yavasoglu, N. Ulku Karabay; Bakan, Buket; Goormaghtigh, Erik; Aktug, HuseyinCellular macromolecules play important roles in cellular behaviors and biological processes. In the current work, cancer (KLN205), normal (MSFs) and mouse embryonic stem cells (mESCs) are compared using ATR-FTIR spectroscopy. Modifications in the composition, concentration, structure and function-related changes in the cellular components were deciphered using the infrared spectra. Our results revealed that cancer and embryonic stem cells are very similar but highly different from the normal cells based on the spectral variations in the protein, lipid, carbohydrate and nucleic acid components. The longest lipid acyl chains exist in mESCs, while cancer cells harbor the lowest lipid amount, short lipid acyl chains, a high content of branched fatty acids and thin cell membranes. The highest cellular growth rate and accelerated cell divisions were observed in the cancer cells. However, the normal cells harbor low nucleic acid and glycogen amounts but have a higher lipid composition. Any defect in the signaling pathways and/or biosynthesis of these cellular parameters during the embryonic-to-somatic cell transition may lead to physiological and molecular events that promote cancer initiation, progression and drug resistance. We conclude that an improved understanding of both similarities and differences in the cellular mechanisms among the cancer, normal and mESCs is crucial to develop a potential clinical relevance, and ATR-FITR can be successfully used as a novel approach to gain new insights into the stem cell and cancer research. We suggest that targeting the cellular metabolisms (glycogen and lipid) can provide new strategies for cancer treatment.Öğe L-glutamic acid-g-poly hydroxyethyl methacrylate nanoparticles: acute and sub-acute toxicity and biodistribution potential in mice(Sciendo, 2023) Bakan, Buket; Oltulu, Fatih; Yıldırım, Yeliz; Yavaşoğlu, Altuğ; Akgol, Sinan; Karabay Yavaşoğlu, Nefise ÜlküThe aim of this safety study in mice was to determine in vivo toxicity and biodistribution potential of a single and multiple doses of L-glutamic acid-g-p(HEMA) polymeric nanoparticles as a drug delivery system. The single dose did not cause any lethal effect, and its acute oral LD50 was >2.000 mg/kg body weight (bw). Multiple doses (25, 50, or 100 mg/kg bw) given over 28 days resulted in no significant differences in body and relative organ weights compared to control. These results are supported by biochemical and histological findings. Moreover, nanoparticle exposure did not result in statistically significant differences in micronucleus counts in bone marrow cells compared to control. Nanoparticle distribution was time-dependent, and they reached the organs and even bone marrow by hour 6, as established by ex vivo imaging with the IVIS (R) spectrum imaging system. In conclusion, L-glutamic acid-g-p(HEMA) polymeric nanoparticles appear biocompatible and have a potential use as a drug delivery system.Öğe Preparation of a Tc-99m-labeled graft polymer and its in vitro and in vivo evaluation(Springer, 2021) Avcibasi, Ugur; Turkyarar, Taner; Karadag, Aysegul; Bakan, Buket; Yavasoglu, Nefise Ulku Karabay; Kusat, Kevser; Akgol, SinanThe aim of this study is the synthesis of a novel Tc-99m-labeld graft polymer and the biological evaluation of its in vitro and in vivo properties. To this end, a L-proline-graft-poly(HEMA) was prepared and labeled with Tc-99m. The radiochemical yield of approximately the Tc-99m-labeled compound amounted to 97 +/- 2.3%. The cytotoxicity test revealed no cytotoxic effect after a 24- and 48-h incubation. The results of the hemolysis test showed that hemolysis was non-toxic with an effect level of less than 2%. Subsequently, the biodistribution in healthy rats was determined. High accumulation of the polymer was observed in the pancreas, thyroid and prostate.Öğe Receptor mediated targeting of EGF-conjugated alginate-PAMAM nanoparticles to lung adenocarcinoma: 2D/3D in vitro and in vivo evaluation(Elsevier, 2024) Ilhan-Ayisigi, Esra; Saglam-Metiner, Pelin; Sanci, Ebru; Bakan, Buket; Yildirim, Yeliz; Buhur, Aylin; Yavasoglu, AltugCarboplatin (cis-diamine (1,1-cyclobutandicarboxylaso)-platinum (II)) is a second-generation antineoplastic drug, which is widely used for chemotherapy of lung, colon, breast, cervix, testicular and digestive system cancers. Although preferred over cisplatin due to the lower incidence of nephrotoxicity and ototoxicity, efficient carboplatin delivery remains as a major challenge. In this study, carboplatin loaded alginate- poly(amidoamine) (PAMAM) hybrid nanoparticles (CAPs) with mean sizes of 192.13 +/- 4.15 nm were synthesized using a microfluidic platform, then EGF was conjugated to the surface of CAPs (EGF-CAPs) for the receptor-targeted delivery. Hence, increased FITC+ cell counts were observed in A549 spheroids after EGF-CAP treatment compared to CAP in the 3D cellular uptake study. As such, the cytotoxicity of EGF-CAP was approximately 2-fold higher with an IC50 value of 35.89 +/- 10.37 mu g/mL compared to the CAPs in A549 spheroids. Based on in vivo experimental animal model, anti-tumor activities of the group treated with CAP decreased by 61 %, whereas the group treated with EGF-CAP completely recovered. Additionally, EGF-CAP application was shown to induce apoptotic cell death. Our study provided a new strategy for designing a hybrid nanoparticle for EGFR targeted carboplatin delivery with improved efficacy both in vitro and in vivo applications.Öğe Synthesis, characterization and toxicity assessment of a new polymeric nanoparticle, L-glutamic acid-g-p(HEMA)(Elsevier Ireland Ltd, 2020) Bakan, Buket; Gulcemal, Suleyman; Akgol, Sinan; Hoet, Peter H. M.; Yavasoglu, N. Ulku KarabayThe toxic effects of poly(HEMA)-based polymeric nanoparticles must be analyzed before their biomedical applications as drug delivery systems. the aim of the study was to characterize and evaluate the toxicity for its biocompatibility of a newly synthesized L-glutamic acid-g-p(HEMA) polymeric nanoparticle the nanoparticle was synthesized with surfactant-free emulsion polymerization and grafting techniques. Grafting efficiency was estimated at 58%. the nanoparticle shape was verified as nearly spherical by scanning electron microscopy. Atomic force microscopy images showed a rough surface topography. the nanoparticle had an average size of similar to 194.6 nm on zeta analysis, and the zeta potential value was -18 mV. Fourier transformed infrared spectroscopy revealed spectra from 750 to 4000 cm(-1) and characteristic peaks of stretching bands. the swelling ratio was 46%. With 24-h exposure, p(HEMA) and L-glutamic acid-g-p(HEMA) did not have cytotoxic effects on a human bronchial epithelial cell line (16HBE) and human monocyte cell line by water-soluble tetrazolium salt 1 (WST-1) assay and lactate dehydrogenase assay (LDH). It did not show genotoxic potential by comet assay and did not have mutagenic effects on Salmonella typhimurium TA98, TA100, TA1535 and TA1537 strains by Ames test. the nanoparticle at 160 mu g/ml showed 2% hemolytic activity on erythrocytes. on cell migration assay, the percentage closure difference between exposed and control cells was estimated at 21%. We found no irritation effect on Hen's egg test-chorioallantoic membrane test. We determined that the polymeric nanoparticle L-glutamic acid-g-p(HEMA) was biocompatible and has potential for use in a drug delivery system.Öğe Synthesis, characterization, toxicity and in vivo imaging of lysine graft polymeric nanoparticles(Springer, 2019) Bakan, Buket; Kayhan, Ceren Turkcan; Karayildirim, Cinel Koksal; Dagdeviren, Melih; Gulcemal, Suleyman; Yildirim, Yeliz; Akgol, Sinan; Yavasoglu, N. Ulku KarabayPolymeric nanoparticles are commonly used in several biological applications. There are limited number of studies on the toxicity and potential effectiveness of polymeric nanoparticles to need for further study on polymer science. The aim of the study was to investigate characterization, in vitro, in vivo toxicity and biological distribution of Lys-graft-p(HEMA) polymeric nanoparticle. The characterization analyses showed that Lys-graft-p(HEMA) had an average size of around 171 nm and zeta potential was -22.6 mV. The sample was recorded from 750 to 4000 cm(-1) in FTIR spectroscopy and the characteristic peaks of stretching band were observed in the spectrum. The polymeric nanoparticle did not show any cytotoxic effect on human embryonic kidney 293 healthy cell line (HEK 293, ATCC-CRL-1573) after 24 and 48 h of exposure. The nanoparticle did not cause mutation effects on Salmonella typhimurium TA 98, TA 100, TA 1535 and TA 1537 strains. In addition, it has not hemolitic activity on rabbit erythrocytes at applied concentration and no lethality was observed with single oral dose toxicity test. FITC-Lys-graft-p(HEMA) were observed on different organs such as liver, kidney, heart, lung and large intestine at 6. hours by in vivo imaging system. These results reveal that Lys-graft-p(HEMA) polymeric nanoparticles can be used as a potential drug carrier system because of its biocompatibility.
