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Investigation of the biocompatibility and in vivo wound healing effect of Cotinus coggygria extracts
(Ankara Univ, 2024) Bozkaya, Esra; Türk, Mustafa; Ekici, Hüsamettin; Karahan, Siyami
Cotinus coggygria is widely recognized its antiseptic, anti-inflammatory, antimicrobial, antihemorrhagic, and wound-healing properties. In this, aimed to evaluate the phenolic contents, cytotoxicity/proliferation, hemolytic, antimicrobial, genotoxic, apoptotic, necrotic activities, and in vivo wound healing effects of C. coggygria, , a plant species known to have beneficial effects on wound healing. TOF-LC/MS analyzes revealed that the methanol extract of C. coggygria leaves contained flavonoids and phenolic compounds such as gallic acid (18.5 mg/kg), catechin (4.6 mg/kg), protocatesic acid (0.6 mg/kg), vanillic acid (8.4 mg/kg), ellagic acid (0.1 mg/kg), rosmarinic acid (0.1 mg/kg), quercetin (15 ppb) and C. coggygria stems contained such as gallic acid (24.6 mg/kg), catechin (155.1 mg/kg), chlorogenic acid (1.9 mg/kg), 4hydroxybenzoic acid (383.3 mg/kg), rutin (2.5 mg/kg), ellagic acid (15.1 mg/kg), apigenin 7-glycoside (10.5 mg/kg), rosmarinic acid (0,4 mg/kg), quercetin (15.2 mg/kg), naringenin (279.1 mg/kg). Consequently, C. coggyria has a positive effect on wound healing with antibacterial properties, particularly against E. coli, and without cytotoxic, genotoxic, or hemolytic effects at test concentrations. In the in vivo burn model, wounds treated with leaf and stem extracts healed faster than the control group. Thus, C. coggygria is an effective plant for wound healing with antibacterial properties, particularly against E. coli, and without cytotoxic, genotoxic, and hemolytic effects.
Effects of functional poly(ethylene terephthalate) nanofibers modified with sericin-capped silver nanoparticles on histopathological changes in parenchymal organs and oxidative stress in a rat burn wound model
(Ankara Univ, 2023) Şahin, Yaşar; Gün Gök, Zehra; Alçığır, Mehmet Eray; Çınar, Miyas
In this study, it was aimed to investigate the effect of a poly(ethylene terephthalate)-g-poly(hydroxyethyl methacrylate) (PET-g-HEMA) nanofiber wound dressing modified with sericin-coated silver nanoparticles (S-AgNPs) on internal organs, oxidative stress, and biochemical parameters. To establish a burn model, the backs of anesthetized rats were shaved and then third-degree burns were created with a round-bottomed stainless steel rod 2 cm in diameter kept in 100 degrees C water for 20 seconds. The wounds of the negative control group (G1) were covered with standard bandages; the wounds of the positive control group (G2) were covered with silvercel, used as burn wound material; and the wounds of the experimental group (G3) were covered with PET-based dressing material. Histopathological changes in organs (liver, kidneys, heart, pancreas, lungs), total oxidant status (TOS), total antioxidant status (TAS), nitric oxide (NO), and biochemical parameters (serum aspartate aminotransferase [AST], alanine aminotransferase [ALT], gamma glutamyl transpeptidase [GGT], creatine kinase, lactate dehydrogenase [LDH], total protein, albumin, globulin, urea) were examined. Compared with the G1 group, plasma AST, ALT, and GGT levels were found to be significantly decreased in G2 and G3 (P<0.001). Plasma TAS was found to be significantly increased in G2 and G3 compared to G1 (P<0.05). Compared to the G1 group, degenerative and necrotic changes in the liver, kidneys, and pancreas were found to be significantly reduced in G2 and G3 (P<0.05). In conclusion, this work demonstrates that the synthesized PET-based wound dressing material has the capacity to be used commercially.
In vivo imaging/detection of MRSA bacterial infections in mice using fluorescence labelled polymeric nanoparticles carrying vancomycin as the targeting agent
(TAYLOR & FRANCIS LTD, 2020) Dizaji, Araz Norouz; Ding, Dan; Kutsal, Tulin; Turk, Mustafa; Kong, Deling; Piskin, Erhan
This study aims to develop fluorescence labelled polymeric nanoparticle (NP) carrying vancomycin as the targeting agent for in vivo imaging of Methicillin-resistant Staphylococcus aureus bacterial infections in animal models. Maleimide functionalized 1,2-distearoyl-sn-glycero-3-phosphoethanolamine-N-[maleimide (polyethylene glycol)-2000] as the main was carrier matrix to prepare the NPs. A fluorescence probe, namely, poly[9,9 '-bis (6 ''-N,N,N-trimethylammonium) hexyl) fluorene-co-alt-4,7-(2,1,3-benzothiadiazole) dibromide] was encapsulated within these NPs by ultrasonication successfully. UV-Vis spectro- photometry of the NPs showed the characteristic shifting on the peak of conjugated polymers indicating successful packaging of this compound with lipid bilayers in nanoscales. Zeta-sizer and TEM analysis showed that the prepared NPs have a diameter of 80-100 nm in a narrow size distribution. Thiolated vancomycin was synthesized and attached to the NPs as the targeting agent. FTIR and MALDI-TOF spectroscopy analysis confirmed the immobilization. The specific targeting properties of the vancomycin conjugated NPs to the target bacteria were first confirmed in in vitro bacterial cultures in which Escherichia coli was the non-target bacteria - using confocal microscopy and TEM. Imaging of bacterial infections in vivo was investigated in mice model using a non-invasive live animal fluorescence imaging technique. The results confirmed that bacterial infections can be detected using these novel polymeric NPs carrying fluorescence probes for imaging and vancomycin as the targeting agent - in vivo successfully.
Hydroxyapatite-based nanoparticles as a coating material for the dentine surface: An antibacterial and toxicological effect
(ELSEVIER SCI LTD, 2020) Erdem, Umit; Dogan, Mustafa; Metin, Aysegul U.; Baglar, Serdar; Turkoz, Mustafa B.; Turk, Mustafa; Nezir, Saffet
In this study, nano sized hydroxyapatite (nHAp) and Ag(I) doped hydroxyapatite (Ag-nHAp) particles were synthesized by the precipitation method and used as a coating material for remineralization on caries-affected dentine samples. Characterization studies of both the synthesized hydroxyapatite-based particles and the coated dentine samples were performed using instrumental techniques such as SEM and FFIR, and then toxicity and antibacterial properties were also evaluated. It was observed that dentine samples were effectively coated by both nHAp and Ag center dot nHAp particles which have no toxic effects. Furthermore, the costing of nano-hydroxyapatite on dentine samples positively contributed to the viability of L929 fibroblast cells and also provided an antibacterial effect against to bacteria such as S. mutants, C. albicans and E. coli bacteria that are most frequently caused caries in the teeth. While all type of bacteria was eliminated by the nHAp coated dentine samples at 24th, Ag-nHAp coated dentine samples removed to all bacteria type at 1st.
The Pimpled Gold Nanosphere: A Superior Candidate for Plasmonic Photothermal Therapy
(DOVE MEDICAL PRESS LTD, 2020) Nasseri, Behzad; Turk, Mustafa; Kosemehmetoglu, Kemal; Kaya, Murat; Piskin, Erhan; Rabiee, Navid; Webster, Thomas J.
Background: The development of highly efficient nanoparticles to convert light to heat for anti-cancer applications is quite a challenging field of research. Methods: In this study, we synthesized unique pimpled gold nanospheres (PGNSs) for plasmonic photothermal therapy (PPTT). The light-to-heat conversion capability of PGNSs and PPTT damage at the cellular level were investigated using a tissue phantom model. The ability of PGNSs to induce robust cellular damage was studied during cytotoxicity tests on colorectal adenocarcinoma (DLD-1) and fibroblast cell lines. Further, a numerical model of plasmonic (COMSOL Multiphysics) properties was used with the PPTT experimental assays. Results: A low cytotoxic effect of thiolated polyethylene glycol (SH-PEG400-SH-) was observed which improved the biocompatibility of PGNSs to maintain 89.4% cell viability during cytometry assays (in terms of fibroblast cells for 24 hrs at a concentration of 300 mu g/mL). The heat generated from the nanoparticle-mediated phantom models resulted in Delta T=30 degrees C, Delta T=23.1 degrees C and Delta T=21 degrees C for the PGNSs, AuNRs, and AuNPs, respectively (at a 300 mu g/mL concentration and for 325 sec). For the in vitro assays of PPTT on cancer cells, the PGNS group induced a 68.78% lethality (apoptosis) on DLD-1 cells. Fluorescence microscopy results showed the destruction of cell membranes and nuclei for the PPTT group. Experiments further revealed a penetration depth of sufficient PPTT damage in a physical tumor model after hematoxylin and eosin (H&E) staining through pathological studies (at depths of 2, 3 and 4 cm). Severe structural damages were observed in the tissue model through an 808-nm laser exposed to the PGNSs. Conclusion: Collectively, such results show much promise for the use of the present PGNSs and photothermal therapy for numerous anti-cancer applications.
Synthesis and characterization of antibacterial drug loaded beta-tricalcium phosphate powders for bone engineering applications
(SPRINGER, 2020) Topsakal, Aysenur; Ekren, Nazmi; Kilic, Osman; Oktar, Faik N.; Mahirogullari, Mahir; Ozkan, Ozan; Sasmazel, Hilal Turkoglu
Powders of beta-tricalcium phosphate [beta-TCP, beta-Ca-3(PO4)(2)] and composite powders of beta-TCP and polyvinyl alcohol (PVA) were synthesized by using wet precipitation methods. First, the conditions for the preparation of single phase beta-TCP have been delineated. In the co-precipitation procedure, calcium nitrate and diammonium hydrogen phosphate were used as calcium and phosphorous precursors, respectively. The pH of the system was varied in the range 7-11 by adding designed amounts of ammonia solution. The filtered cakes were desiccated at 80 degrees C and subsequently calcined at different temperatures in the range between 700-1100 degrees C. Later on, rifampicin form II was used to produce drug-loaded beta-TCP and PVA/beta-TCP powders. All the synthesized materials have been characterized from morphological (by scanning electron microscopy) and structural-chemical (by X-ray diffraction and Fourier transform infrared spectroscopy) point of view. The drug loading capacity of the selected pure beta-TCP powder has been assessed. The biological performance (cytocompatibility in fibroblast cell culture and antibacterial efficacy against Escherichia coli and Staphylococcus aureus) has been tested with promising results. Application perspectives of the designed drug-bioceramic-polymer blends are advanced and discussed. [GRAPHICS] .
Production of 2-hydroxyethyl methacrylate-g-poly(ethylene terephthalate) nanofibers by electrospinning and evaluation of the properties of the obtained nanofibers
(WILEY, 2020) Gok, Zehra Gun; Inal, Murat; Bozkaya, Ogun; Yigitoglu, Mustafa; Vargel, Ibrahim
Nanofiber production was investigated from poly(ethylene terephthalate) (PET) polymers functionalized with hydroxyethyl methacrylate (HEMA) by grafting of HEMA monomers onto the PET fibers. HEMA grafted PET (PET-g-HEMA) copolymers were analyzed by scanning electron microscopy, Fourier transform infrared spectroscopy, nuclear magnetic resonance spectroscopy. PET and PET-g-HEMA were dissolved in trifluoroacetic acid and nanofibers were obtained by electrospinning. It was found that the PET and PET-g-HEMA polymers having grafting yield 20 and 55% could be converted to continuous, smooth, and beadles nanofibers. For characterization of the nanofiber membranes, thermogravimetric analysis, differential scanning calorimeter analysis, surface contact angle measurement, porosity analysis, and mechanical tests were applied. When compared with the original PET nanofibers, the thermal properties and degradation process of PET-g-HEMA nanofibers changed according to the amount of HEMA present in the structure of nanofibers. The contact angles of the nanofibers obtained from PET-g-HEMA polymers decreased whereas the water retention ability of the nanofibers increased compared to original PET nanofibers. The porosity of PET-g-HEMA nanofibers was found be high compared to PET nanofibers and whereas the mechanical properties of PET was higher than PET-g-HEMA nanofibers. The obtained nanofibers can be used in many fields such as biomaterial applications.
Phosphorus-nitrogen compounds. Part 48. syntheses of the phosphazenium salts containing 2-pyridyl pendant arm: structural characterizations, thermal analysis, antimicrobial and cytotoxic activity studies
(NATL INST SCIENCE COMMUNICATION-NISCAIR, 2020) Elmas, Gamze; Okumus, Aytug; Kilic, Zeynel; Ozbeden, Pelin; Acik, Leyla; Tunali, Beste Cagdas; Turk, Mustafa
The phosphazenium salts (protic ionic liquids, PILs/protic molten salts, PMOSs) (6a-6d and 7a) of the free phosphazene bases (4a-4d and 5a) have been prepared by the reactions of the corresponding cyclotriphosphazenes with the bulky gentisic acid. The structures of the PMOS have been evaluated using the elemental analyses, FTIR, H-1, C-13{H-1} and P-31{H-1} NmR data. The molecular and crystal structures of 4a and 6c are established by X-ray crystallography. The thermal properties of the PMOS are determined using TG and DTA techniques. On the other hand, the antimicrobial activities of the free phosphazene bases (4a-4d and 5a-5d) and PMOSs (6a-6d and 7a) are screened against the selected bacteria and yeast strains. The antimicrobial activities of the free phosphazene bases and the PMOSs are compared. The interactions of the phosphazenes and their salts with plasmid DNA are elucidated by the agarose gel electrophoresis. The evaluations of the cytotoxic activities of these compounds are also studied against to L929 fibroblast and breast cancer cells (MDA-MB-231).
Synthesis and biological evaluation of novel urea, thiourea and squaramide diastereomers possessing sugar backbone
(ELSEVIER SCI LTD, 2020) Isilar, Ozer; Bulut, Adnan; Yaglioglu, Ayse Sahin; Demirtas, Ibrahim; Arat, Esra; Turk, Mustafa
A series of novel chiral 14 urea, thiourea and squaramide stereoisomers possessing carbohydrate backbones as well as amide functional groups was synthesized and characterized by their, H-1 NMR, C-13 NMR, FT-IR, HRMS, optical rotation, and melting points. Their antiproliferative activities were investigated against HeLa and PC3 cell lines. The compounds 9, 11 and 12 showed better activities at 25 mu M against PC3 cell line with respect to the standard 5-fluorouracil (5-FU). Especially, the compounds 9 and 11 showed higher activities than the standard 5-FU even at low concentration (5 mu M) against HeLa cell line. IC50 results also confirm these activities. The compounds 9, 10 and 11 have the IC50 values of 1.10 mu M, 1.51 mu M and 1.02 mu M, respectively while 5-FU has 2.51 mu M. Moreover, their cytotoxicity tests have proven that their viabilities were in between 50% and 100%.
Synthesis of Bis(2,2,3,3-tetrafluoro-1,4-butanedialkoxy)-2-trans-6-bis(4-fluorobenzyl)spirocyclotetraphosphazene: Structural Characterization, Biological Activity and DFT Studies
(SPRINGER/PLENUM PUBLISHERS, 2020) Elmas, Gamze; Kilic, Zeynel; Cosut, Bunyemin; Kesan, Gurkan; Acik, Leyla; Cam, Merve; Tunali, Beste Cagdas
The Cl replacement reaction of octachlorocyclotetraphosphazene, N4P4Cl8 (1), with two equimolar amounts of N-(4-fluorobenzyl)-N'-methylpropane-1,3-diamine led to the formation of 4,4,8,8-tetrachloro-2-trans-6-bis-N-(4-fluorobenzyl)-N'-methylpropane-1,3-diamino-cyclotetraphosphazene (2). The reaction of 2 with excess sodium 2,2,3,3-tetrafluoro-1,4-butanedioxide afforded the bis(2,2,3,3-tetrafluoro-1,4-butanedialkoxy)-2-trans-6-bis(4-fluorobenzyespirocyclotetraphosphazene (2a). The elemental analyses, mass spectrum (ESI-MS), FTIR, HSQC, HMBC, H-1, C-13 and P-31 NMR spectral data of 2a were consistent with the proposed structure. The crystal structure of 2a was elucidated by X-ray diffraction method. The spectroscopic data of the molecules (2 and 2a) in the ground state were investigated by the Density Functional Theory (DFT) from the crystal structures. On the other hand, compound 2a was found to be the most active against S. aureus G(+) (MIC value: 125 mu M). Whilst, any antifungal activity of 2a was not observed against C. albicans and C. tropicalis. This compound also exhibits cytotoxic activity against L929 fibroblast and MCF-7 breast cancer cells. The interaction of 2a with pBR322 DNA was researched using gel electrophoresis. It is understood that the change in DNA conformation by interstrand of 2a with A/A and G/G nucleobases in DNA. [GRAPHICS] .
Colloidal stability and biological activity evaluation of microbial exopolysaccharide levan-capped gold nanoparticles
(ELSEVIER, 2020) Akturk, Omer
The main objectives of this study were to explore the suitability of the exopolysaccharide levan, biosynthesized by Bacillus subtilis, to aid in the formation of gold nanoparticles (AuNPs) and to investigate the colloidal stability and in vitro biological activity of this biopolymer-AuNPs complex. AuNPs (mainly spherical, 8-10 nm-sized, and monodispersed) were successfully synthesized in levan concentrations up to 0.5% w/v (L-AuNP0.5) while exposed to ultraviolet C (UVC) irradiation. The increase of levan quantity decreased the size of AuNPs according to Transmission Electron Microscopy (TEM) images and enhanced the colloidal stability significantly. The presence of L-AuNP0.5 at the highest treatment dose (1000 mu g/mL) exhibited substantial cytotoxicity towards L-929 mouse fibroblasts for all incubation periods. Dose-dependent toxicity was observed for the first day while, after this threshold value, medium (100 mu g/mL) and the lowest (10 mu g/mL) treatment doses were non-cytotoxic during 7 days of incubation, implying dose and time-independent cell viabilities ( > 95%) compared to the negative control (complete cell culture medium). There occurred a special surface interaction with cells and LAuNP0.5, especially when the cells were subjected to deliberate starvation periods to increase L-AuNP0.5 internalization via passive and active endocytosis. Scanning Electron Microscopy (SEM) images showed high accumulation of L-AuNP0.5 around or inside the cell membrane after 7 days. Overall, this attribute (high uptake of L-AuNP0.5) could make them promising candidates for prospective cancer therapeutics or drug delivery systems by enabling the cell internalization of anticancer drugs.
Effects of Gold Nanoparticles on Angiogenesis in A Chick Chorioallantoic Membrane Model
(BEZMIALEM VAKIF UNIV, 2020) Cirik, Samet; Elesad, Musa; Basar, Ebrar; Aksu, Elif; Erdem, Muaz; Yildiztekin, Faruk; Menekse, Sinan
Objective: Today, nanotechnology is widely used in many fields because of its ability to alter the structure of molecules at the atomic level. Metallic nanoparticles attracted great attention from researchers because of their unique properties. Based on the notable features of gold nanoparticles (AuNPs), they have long been evaluated as a potential diagnostic tool for several cancers and for drug delivery applications. Angiogenesis is the development of new vessels that support embryonic up growth and critically modulate many biological processes through adulthood. The inhibition of angiogenesis causes regression of development and metastasis of malign tumours. In this study we aim to examine the effects of AuNPs on angiogenesis in an in vivo chick chorioallantoic membrane (CAM) model. Methods: We applied 20 mL concentrations of AuNPs solution to 24 eggs of the CAM on the fifth day. After then, we evaluated results macroscopically on the 6th and 7th days. Results: In our study, we observed that AuNPs induced angiogenesis. Conclusion: We suggest that AuNPs may not be ideal nanoparticles to make biosensors due to increasing angiogenesis during the course of cancers.
In situ synthesis of silver nanoparticles on modified poly(ethylene terephthalate) fibers by grafting for obtaining versatile antimicrobial materials
(SPRINGER, 2020) Gun Gok, Zehra; Demiral, Ayse; Bozkaya, Ogun; Yigitoglu, Mustafa
Because of having high mechanical properties and cheapness of PET textiles, functionalization of them for new properties is an active research area. In the present work, methacrylic acid (MAA)-grafted PET fibers (PET-g-MAA) were obtained by grafting of MAA monomers to PET surface for an antimicrobial material synthesis. The morphologies of the obtained graft copolymers were examined with a scanning electron microscopy (SEM), and the chemical modification after grafting was determined with Fourier-transform infrared spectroscopy (FTIR) analysis. Subsequently, silver ions were adsorbed onto the PET-g-MAA fibers surface and the adsorbed ions to the surface were reduced to silver nanoparticles (AgNPs) by UVC light. The morphology of fiber surfaces modified with MAA and coated with AgNPs was examined by SEM studies, and it was observed that AgNPs were disturbed along the fibers. The presence of silver on the surface was also confirmed by energy-dispersive X-ray spectroscopy (EDS) and energy dispersion X-ray fluorescence spectrometry (EDXRF). The crystalline structure of the original PET fiber, PET-g-MAA fiber and PET-g-MAA fiber modified with AgNPs was investigated by X-ray diffraction (XRD). The thermal properties of the obtained fibers were investigated by thermogravimetric analysis (TGA). The immobilization of AgNPs on the grafted fibers leads to a change on the patterns of TGA curves. The most significant change is the less weight reduction in the temperature range of 200-300 degrees C. Disk diffusion test was performed using Staphylococcus aureus (ATCC 6538) and Escherichia coli (ATCC 25,922) bacteria in order to investigate the antibacterial ability of the obtained fibers, and it was found that the fibers coated with AgNPs had antibacterial effect on both bacterial species. The cytotoxicity of the groups with the best antibacterial properties was determined by MTT test, and the synthesized material did not have cytotoxic effects on L929 fibroblast cells. The material obtained has the potential to be used in antimicrobial applications.
Novel fluorescent coumarin-thiophene-derived Schiff bases: Synthesis, effects of substituents, photophysical properties, DFT calculations, and biological activities
(Elsevier Science Sa, 2019) Yahaya, Issah; Chemchem, Meryem; Aydiner, Burcu; Seferoglu, Nurgul; Tepe, Fulya Erva; Acik, Leyla; Seferoglu, Zeynel
Novel fluorescent coumarin-thiophene appended Schiff bases have been synthesized in good yields (76-89%). The effects of substitution on the fluorescent intensity and solubility of the molecules were examined with experimental techniques. The deprotonation properties of the prepared Schiff bases were examined, in DMSO, by titration of each of the ligands with TBAOH. We also studied the reverse protonation of the fluorophores using TFA. The structural and electronic properties of the neutral and the deprotonated forms of the fluorophores were also examined in the framework of DFT calculations. Also, the cytotoxicity of each of the compounds was tested against L929 fibroblasts and human lung cancer (small cell). Furthermore, the antimicrobial activity of each of the compounds was studied against both Gram-negative and Gram-positive bacterial and fungal species. In the final studies, the plasmid DNA interactions with the compounds were investigated with agarose gel electrophoresis. The thermal properties of all the prepared compounds were determined by thermal gravimetric analysis (TGA) and were found to be thermostable up to at least 335 degrees C.
Biodegradation of 2,4,6-Trinitrotoluene (TNT) with Bacteria Isolated from TNT-polluted Waste Pink Water
(Budapest Univ Technology Economics, 2019) Gok, Zehra Gun; Inal, Murat; Yigitoglu, Mustafa
In this study, bacterial strains that can use TNT as a nitrogen source isolated from TNT contaminated pink water. We isolated 5 bacterial strains and the isolated bacteria were cultured in medium containing TNT and TNT degradation capacities of isolates were determined by spectrophotometric analysis. According to the results of the analysis that have done, 3 bacterial isolates that have high TNT degradation capacity were selected and the isolates were identified with firstly Gram-staining then with 16S rRNA sequence analysis method. According to the sequence of 16S rRNA, water isolates were identified as Stenotrophomonas maltophilia (SU K2), Klebsiella pneumoniae (SU K3), Raoultella planticola (SU K4). During the TNT degradation studies, at the end of 24 h incubation time, in the medium containing 100 mg/L TNT, TNT degradation rate for SU K2, SU K3 and SU K4 were determined 70 %, 96 % and 93 % respectively. 4-aminodinitrotoluene and 2-aminodinitrotoluene accumulations were detected in the culture medium of all isolates as intermediate products formed during the degradation of TNT by HPLC analysis. Additionally, nitrite accumulation was detected in the culture medium of all isolates and the influence of temperature and pH on the degradation of TNT was also investigated. It was determined that SU K2 isolates have the highest TNT degradation capacity at 35 degrees C, the others have at 30 degrees C and all isolates degraded TNT fastest at pH 7. The results of the study show that the new isolates can be useful for the removal of TNT in a wastewater treatment system.
Radiation Enhancement with Polyethyleneimine-Coated Gold Nanoparticles Under MV Photons
(Kare Publ, 2019) Aytac Arslan, Suheyla; Turk, Mustafa
OBJECTIVE Radiotherapy is an essential part of cancer management, and about two-thirds of the patients with cancer receive radiation therapy during their treatment. The healthy structures around the tumor are dose limiting in terms of acute and late toxicity. Radiosensitizers (RSs) can be used to enhance intratumoral dose, thus improving the therapeutic ratio. We aimed to investigate the cytotoxicity on normal and cancer cell lines induced by interaction between MV photon irradiation and polyethyleneimine (PEI)-coated gold nanoparticles (AuNPs). METHODS The effects of different concentrations of AuNPs (0.75 mu g/ml, 0.5 mu g/ml, 0.25 mu g/ml, and only medium) and 2-Gy ionizing radiation (IR) were investigated on the L929 fibroblast, DLD-1 colon, and H1299 lung cancer cell lines. Cytoplasmic and nuclear membranes treated with hematoxylin and eosin and double staining were evaluated with light and fluorescence microscopy. Cytotoxicity was determined with the WST-1 method. RESULTS All particles were spherical in shape with 60.98 nm in size. Cell surviving ratios without AuNPs were 96.34% in L929, 89.68% in DLD-1, and 76.93% in H1299 for a single 2-Gy radiation. These ratios were 94.2%, 62.58%, and 40.52% for L929 cells; 72.70%, 41.15%, and 26.71% for DLD-1 cells; and 34.72%, 28.27%, and 17.84% for H1299 cells at concentrations of 0.25 mu g/ml, 0.5 mu g/ml, and 0.75 mu g/ml AuNPs, respectively. CONCLUSION At increased concentrations, isolated unwanted cytotoxic effects of AuNPs could be observed. Radiosen-sitizing effect of PEI-coated AuNPs depends on cell type and AuNP concentration.
Effects of B2O3 (boron trioxide) on colon cancer cells: our first-step experience and in vitro results
(Tubitak Scientific & Technical Research Council Turkey, 2019) Albuzi, Ozgur; Dulger, Dilek; Tunali, Beste Cagdas; Aydin, Feray; Yalcin, Selim; Turk, Mustafa
Boron oxide (B2O3) is derived from dehydration of boric acid and is a colorless, semitransparent, crystalline compound that is moderately soluble in water. On the other hand, boron oxide is chemically hygroscopic. This gives the molecule the ability to soak up water and adhere to tissues. Boron oxide can be used locally after tumor debulking in inoperable tumors and especially when the twnor-free margin distance cannot be provided. For all these reasons we aimed to evaluate the in vitro test results of B2O3, in terms of cytotoxicity, genotoxicity, apoptosis, and necrotic effects on L929 fibroblast cells and DLD-1 colorectal adenocarcinoma cells. Our studies demonstrated that boron oxide compounds appear to be highly cytotoxic for both cell lines according to WST cell viability assay (44.22% and 18.36% on DLD-1 and L929, respectively). Although no genotoxic effects were observed, boron oxide compounds showed antiproliferative effects for both cell lines. The prepared boron oxide compounds may hold the potential to be applied locally to the remaining tissue after surgery and further research and evaluation will be needed to determine its effectivenesss.
Anti Wnt-1 Monoclonal Antibody's Conjugated with Gold Nanoparticles, Induced Apoptosis on MCF-7 Breast Cancer Cell Lines
(Trans Tech Publications Ltd, 2019) Azar, Mehdi Tayybi; Saglam, Necdet; Turk, Mustafa
Wnt-beta Catenin Pathway has an important role in many cancers. Wnt-1 protein from Wnt protein family that regulate this pathway has a special effect on the development of breast cancer. Monoclonal antibodies attach to metal nanoparticles have an important role in diagnosis and treatment of cancers. In this study, Anti Wnt-1 monoclonal antibody was conjugated to the gold nanoparticles synthesized by Turkevich method. Conjugation was achieved using EDC-NHS method. The density of the monoclonal antibodies that bonded to gold nanoparticles was measured by Roche Cobas Integra 400 Plus device. MCF-7 breast cancer cell line was treated with conjugated nanoparticles for 48 h then Double Staining method was used to detect apoptosis cells. The results showed that inhibition of Wnt-1 protein in extracellular matrix causes apoptosis and gold nanoparticles have a positive effect on Anti Wnt-1 monoclonal antibodies and this positive effect causes apoptosis to increase rate in conjugating nanoparticles.
Phosphorus-nitrogen compounds. Part 44. The syntheses of N,N-spiro bridged cyclotriphosphazene derivatives with (4-fluorobenzyl) pendant arms: Structural and stereogenic properties, DNA interactions, antimicrobial and cytotoxic activities
(Elsevier Science Sa, 2019) Ozturk, Ezel; Okumus, Aytug; Kilic, Zeynel; Kilic, Adem; Kayalak, Hande; Acik, Leyla; Hokelek, Tuncer
Isopropylaminopentachlorocyclotriphosphazene, (N3P3Cl5(NHCHMe2) (1), containing a P-NH group in the alkyl-chain, gives the NN-spirobridged octachlorobiscyclotriphosphazene, [N3P3Cl4(NCHMe2)](2) (2), in the presence of NaH. The reactions of 2 with excess pyrrolidine result in the formation of the fully substituted bridged product 2a. The reactions of 2 with 1:1 and 1:2 equimolar amounts of N-(4-fluorobenzyl)N'methylethane-1,2-diamine and N-(4-fluorobenzyl)-N'methylpropane-1,3-diamine produce the (4-fluorobenzyl) pendant armed monospiro (2b and 2c) and dispiro (2f and 2g) products. These compounds react with excess pyrrolidine to form stable, fully substituted cyclotriphosphazenes (2d, 2e, 2h and 2i). The structures of 2a and 2f are determined by X-ray crystallography. The stereogenic properties of 2a and 2f having four potential stereogenic P-centers are investigated by crystallography. The monospiro (2b-2e) and dispiro (2f-2i) products have one and two equivalent chiral centers, respectively. The dispiro derivatives may have two meso (trans-trans and cis-cis) and two racemate (trans-cis and cis-trans) mixtures. However, the structure of 2f is found to be as trans-trans (meso) isomer. Besides, in vitro antimicrobial and cytotoxic activities of 2d and 2h are evaluated. The compounds exhibit significant growth inhibitory effects on E. coli and B. cereus bacteria. Compound 2d has high anticancer and apoptotic activities.
Transscleral Delivery of Bevacizumab-Loaded Chitosan Nanoparticles
(Amer Scientific Publishers, 2019) Ugurlu, Nagihan; Asik, Mehmet Dogan; Cakmak, Hasan Basri; Tuncer, Sema; Turk, Mustafa; Cagil, Nurullah; Denkbas, Emir Baki
Purpose: The aim of this study was to synthesize bevacizumab-loaded nanoparticles and evaluate their effects on the treatment of posterior segment diseases via subtenon injections. Methods: Bevacizumab-loaded chitosan nanoparticles (BLCNs) were synthesized by the ionic gelation method, and their physicochemical characteristics and in vitro release profile were studied. The BLCNs were characterized using atomic force microscopy (AFM), FTIR spectroscopy, dynamic light scattering, and scanning electron microscopy. The BLCNs were delivered into rabbits' eyes via posterior subtenon injections. An immunohistochemical evaluation of the ocular tissues was performed, and the vitreous humor and serum bevacizumab levels were measured by ELISA. Results: Bevacizumab-loaded chitosan nanoparticles with a diameter of 80 to 380 nm were prepared and characterized. In vitro studies showed that after the first 5 days of the experiment, a significant increase in the drug release maintained the desired drug dosage for 3 weeks. Immunohistochemical in vivo studies revealed that there were BLCNs penetrating through the sclera. Furthermore, the intravitreal bevacizumab concentration reached a maximum concentration of 18 mu g/ml, and it decreased to 6 mu g/ml after only a week. Conclusion: The results revealed that subtenon injection of BLCNs is a promising alternative to intravitreal injections. In addition to the ELISA studies, immunohistochemical experiments confirmed that BLCNs enable transscleral bevacizumab penetration, and BLCN usage may provide the required bevacizumab levels for the treatment of posterior segment diseases.

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