BODIPY-conjugated chitosan nanoparticles as a fluorescent probe

Recently, development of fluorescent nanoparticle-based probes for various bioimaging applications has attracted great attention. This work aims to develop a new type fluorescent nanoparticle conjugate and evaluate its cytotoxic effects on A549 and BEAS 2B cell lines. Throughout the study, ionically crosslinked chitosan nanoparticles (CNs) were conjugated with carboxylated 4,4-difluoro-4-bora-3a,4a-diaza-s-indacene (BODIPY-COOH). The results of conjugates (BODIPY-CNs) were investigated with regard to their physic-chemical, optical, cytotoxic properties and cellular internalization. The morphology of BODIPY-CNs was found to be spherical in shape and quite uniform having average diameter of 70.25 ± 11.99 nm. Cytotoxicty studies indicated that although BODIPY-COOH itself was quite toxic on both A549- and BEAS 2B-treated cells, CNs increased the cell viability of both cell lines via conjugation to BODIPY-COOH fluorescent molecule up to 67% for A549 and 74% for BEAS 2B cells. These results may suggest a possible utilization of the new fluorescent nanoparticle-based probe for bioimaging in biology and medicine

Prostat ve meme kanseri fototermal tedavisi için plazmonik nanoyapıların geliştirilmesi

Thesis (Doctoral)--Izmir Institute of Technology, Materials Science and Engineering, Izmir, 2019Includes bibliographical references (leaves: 105-118)Text in English; Abstract: Turkish and EnglishThe aim of this thesis is to synthesize gold nanorods (AuNRs) and lipid-stabilized nanobubbles containing AuNRs and investigate the potential of these plasmonic nanostructures as photothermal therapy agents for breast and prostate cancer through in vitro cell culture experiments. For this aim, firstly, AuNRs were synthesized at varying aspect ratios (ARs) and characterized via several techniques including UV-Vis/NIR spectroscopy, scanning electron microscopy (SEM), atomic force microscopy (AFM), inductively coupled plasma-mass spectroscopy (ICP-MS), electrophoretic light scattering (ELS) and X-ray photoelectron spectroscopy (XPS). The surface of AuNRs was modified with a biocompatible polymer, poly(ethylene glycol) (PEG), via ligand exchange method. Cytotoxicity, cell uptake and photothermal effects of AuNRs were investigated via in vitro cell culture experiments using human prostate cancer (DU 145) and epithelial (RWPE-1), breast cancer (MCF7) and epithelial (MCF 10A) cell lines. It was concluded that AuNRs (AR=4.0) were superior than AuNRs (AR=7.0) in terms of cell viability and photothermal effect. Separately, a non-commercial antibody (Ab) targeting a specific sialic acid derivative on the plasma membrane of DU 145 and MCF7 cancer cells was conjugated to AuNRs. Conjugations were characterized with the same techniques and investigated via in vitro cytotoxicity and cell uptake experiments. The Ab-conjugated AuNRs displayed the capability of selective targeting prostate cancer cells. Additionally, lipid-stabilized AuNRs and lipid-stabilized nanobubbles containing AuNRs (AuNBs) were synthesized for the first time and characterized using UV-Vis/NIR spectroscopy, SEM, ICP-MS and ELS techniques. Lipid-stabilized AuNRs were successfully synthesized using varying lipid mixtures instead of cationic, toxic surfactant. Separately, AuNBs were synthesized by combining PEG modified AuNRs with DPPC: DSPE-PEG lipid film under sonication and gas stream. AuNBs showed the same or significantly lower toxicity depending on the cell types and the same photothermal effect with respect to AuNRs (AR=4.0) upon irradiation under laser at 808 nm.Bu tezin amacı, altın nanoçubukları (AuNRs) ve altın nanoçubukları içeren lipit stabilize edilmiş nanobalonları sentezlemek ve bu plazmonik nanoyapıların, in vitro hücre kültürü deneyleri aracılığıyla meme ve prostat kanseri için fototermal terapi maddeleri olarak potansiyelini araştırmaktır. Bu amaçla, ilk olarak, altın nanoçubuklar değişen boy-en oranlarında sentezlendi ve UV-Vis/NIR spektroskopisi, taramalı elektron mikroskobu (SEM), atomik kuvvet mikroskobu (AFM), indüktif olarak eşleşmiş plazma kütle spektroskopisi (ICP-MS), elektroforetik ışık saçılımı (ELS) ve X-ışını fotoelektron spektroskopisi (XPS) dahil olmak üzere çeşitli tekniklerle karakterize edildi. Altın nanoçubukların yüzeyi, ligand değişim metodu ile biyouyumlu bir polimer olan poli(etilen glikol) (PEG) ile modifiye edildi. Altın nanoçubukların sitotoksisitesi, hücre alımı ve fototermal etkileri, insan prostat kanser (DU 145) ve epitel (RWPE-1), meme kanser (MCF7) ve epitel (MCF 10A) hücre hatları kullanılarak in vitro hücre kültürü deneyleri ile araştırıldı. Hücre canlılığı ve fototermal etki açısından boy-en oranı 4 olan altın nanoçubukların boy-en oranı 7 olandan daha üstün olduğu sonucuna varıldı. Ayrı olarak, DU 145 ve MCF7 kanser hücrelerinin plazma zarı üzerinde spesifik bir sialik asit türevini hedef alan bir antikor, altın nanoçubuklara konjuge edildi. Konjugasyonlar aynı teknikler ile karakterize edildi ve in vitro sitotoksisite ve hücre alımı deneyleri ile araştırıldı. Antikor ile konjuge altın nanoçubuklar prostat kanseri hücrelerini seçici hedefleme yeteneği göstermiştir. Ek olarak, lipit stabilize edilmiş altın nanoçubuklar ve altın nanoçubukları içeren lipit stabilize edilmiş nanobalonlar ilk kez sentezlendi ve UV-Vis/NIR spektroskopisi, SEM, ICP-MS ve ELS yöntemleri kullanılarak karakterize edildi. Katyonik, toksik yüzey aktif madde yerine çeşitli lipit karışımları kullanılarak lipit stabilize altın nanoçubuklar başarıyla sentezlendi. Ayrıca, altın nanobalonlar sonikasyon ve gaz akışı altında PEG modifiye altın nanoçubukların DPPC: DSPE-PEG lipit filmi ile birleştirilmesiyle sentezlendi. Altın nanobalonlar boy-en oranı 4 olan altın nanoçubuklara göre, hücre tiplerine bağlı olarak önemli ölçüde daha düşük veya aynı toksisite ve 808 nm lazer ışıması altında aynı fototermal etki gösterdi.TUBITAK/TBAG/112T507, TUBITAK/MAG/213M673, TUBITAK/MFAG/117F18

Gold nanorod encapsulated bubbles

A simple method has been described for synthesizing gold nanorods (GNRs) encapsulated bubbles in a controlled manner. The method involves the use of nitrogen gas in the seed-mediated synthesis method routinely used for synthesis of GNRs. Control over the morphology of the nanostructures was achieved by nitrogen gas flow. The synthesized structures were examined by UV-Vis Spectroscopy, Scanning Electron Microscopy (SEM) and Atomic Force Microscopy (AFM). New structures of this type could conceivably serve as plasmonic biosensors, nanodevices and photothermal theranostics with dual modality imaging functionality. © The Royal Society of Chemistry 2015.TUBITAK (112T507

Intensive Care Management of a Case of Cardiac Arrest Following Ketiapine Use

Quetiapine is an antipsychotic commonly used in treatment of depression, bipolar disorders and schizophrenia. Quetiapine interacts with several receptors present in the central nervous system and therefore may cause diverse side effects like somnolence, coma or hyperglycemia. By prolonging QT interval, quetiapine may predispose the patient to tachycardia and other cardiac dysrhythmias and even cardiac arrest. Due to its antagonism on histaminergic receptors, quetiapine may cause respiratory depression and coma, necessitating mechanical ventilation support. On this paper, we discussed the management of an 80 year old male who is suspected to present with coma following quetiapine administration

Ventilator-associated pneumonia rate and causative microorganisms in an anesthesia intensive care unit

Amaç: Yoğun Bakım Ünitelerinde en sık görülen nozokomiyal enfeksiyon pnömonidir. Nozokomiyal pnömonilerin önemli kısmını oluşturan ventilatör ilişkili pnömoniler (VİP) önemli morbidite ve mortalite nedenidir. VIP oranı ve hızının belirlenerek enfeksiyon koruma önlemlerinin sürdürülmesi, etkenlerinin ve duyarlılıkların belirlenerek tedavi seçiminin bu doğrultuda yapılması gerekir. Yöntemler: YBÜ’ne yatırılarak takip ve tedavi edilen hastalar ileriye dönük, hastaya ve laboratuvar verilerine dayalı aktif sürveyans yöntemiyle izlenmiştir. Hastane enfeksiyonu tanısı, Centers for Disease Control and Prevention (CDC) kriterlerine göre konulmuştur. Enfeksiyon hızları ve alet kullanım oranları ulusal enfeksiyonları sürveyans kontrol birimi (UHESKB) gerekliliklerine uygun sürveyans sistemi önerilerine göre hesaplanmıştır. Bulgular: Bu çalışmada, hastanemiz reanimasyon yoğun bakım ünitesinde Ocak 2011- 2012 tarihleri arasında 2 günün üzerinde yatan 252 hastada gelişen ve tümünde mekanik ventilatör uygulaması olan 24 pnömoni olgusu incelendi. Ventilatör kullanım oranının % 58 olduğu yoğun bakım ünitesinde 1000 hasta gününde VIP hızı 16,49 olarak tesbit edildi. Hastalardan endotrakeal aspirat yöntemi ile alınan örneklerden izole edilen etkenler değerlendirildiğinde; olguların 18 (% 75) inde tek mikroorganizma 6 (%25) inde iki ve ikiden fazla izole edildi. Bu suşların 27’si (%79,4) gram-negatif bakteri iken 5’i (%14,7) gram-pozitif bakteri, ikisi (%5.8) Candida spp. idi.Gram-negatif etken olarak en sık Acinetobacter spp. 10(%29.4) Acinetobacter baumannii 6(%17.6) elde edilirken bunu Pseudomonas aeruginosa 4 (%11.7), Pseudomonas spp. 4(%11.7), Klebsiella spp. 3(%8.8) takip etmiştir. Gram-pozitif etken olarak da MRSA 2(%5.8) , MRKNS 3 (%8.8) izole edilmiştir. Gram-negatif etkenlerin antibiyotiklere duyarlılıkları incelendiğinde; Acinetobacter suşlarının imipeneme %90, siprofloksasine %60, amikasine %57 dirençli olduğu, seftazidim, netilmisin, kolitsin, tigesikline %100 duyarlı olduğu , diğer gram negatif etkenlerin karbapenemlere %100, siprofloksasine %85 duyarlılğını koruduğu tesbit edilmiştir. Sonuçlar: Görülen mikroorganizma ve elde ettiğimiz duyarlılık sonuçlarına göre, hastanemiz yoğun bakım ünitesinde yatan hastalarda ampirik tedavi gram-negatif etkenlere yönelik düşünülmeli ve karbapenem dirençli Acinetobacter suşların varlığı durumu da göz önüne alınarak kombine tedaviler uygulanmalıdır.Objective: Pneumonia is the most common nosocomial infection encountered in intensive care units. Pneumonia mostly occurs in form of ventilator-associated pneumonia (VAP) which is a maor cause of mortality and morbidity. Therefore, VAP rate should be determined while employing well grounded infection prevention measures. Also causative microorganisms and their susceptibilities should be determined to guide the antibiotic therapy. Methods: Intensive care unit patients were prospectively surveyed in terms of nosoxomial infections through active surveillance methods. Centers for Disease Control and Prevention (CDC) criterias were used in detecting nosocomial infections. İnfection rates and cathehterization rates were calculated according to guidelines of Turkish National İnfection Surveillance Control Group (UHESKB). Results: A total of 252 patients treated for longer than 48 hours in Anesthesia Intensive care Unit during January 2011 and January 2012 were surveyed. We detected VAP in 24 patients, all of whom received mechanical ventilator support. Mechanical ventilator usage rate was 58% and VAP rate was 16.49 in 1000 patient-ventilator days. Cultures of endotracheal aspiration samples showed that 18 (75%) of cases contained a single microorganism whereas 6 (25%) of cases contained two or more microorganisms. Twenty-seven (79.4%) of these microorganisms were gram-negative bacteria, 5 (14.7%) were gram-positive bacteria and 2 (5.8%) were candida species. Most commonly cultured gram-negative bacteria were Acinetobacter spp. 10 (29.4%), Acinetobacter baumannii 6 (17.6%), Pseudomonas aeruginosa 4 (11.7%%), Pseudomonas spp. 4 (11.7%) and Klebsiella spp. 3 (8.8%). Gram-positive microorganisms were MRSA 2 (5.8%) and MRKNS 3 (8.8%). Susceptibility tests showed that Acinetobacter species were resistant to imipeneme by 90%, ciprofloxacine by 60%, amikasine by 57%, and were totally susceptible to seftazidim, netilmisin, kolitsin and tigesikline. Other gram-negative bacteria were susceptible to carbapenems by 100%, ciproflxacine by 85%. Conclusion: Culture and susceptibility test results showed that ampirical antibiotherapy in our intensive care unit should be against gram-negative bacteria and concerning carbapeneme resistant Acinetobacter species, combination therapies should be employed

Few-layer MoS2 as nitrogen protective barrier

We report experimental and theoretical investigations of the observed barrier behavior of few-layer MoS2 against nitrogenation. Owing to its low-strength shearing, low friction coefficient, and high lubricity, MoS2 exhibits the demeanor of a natural N-resistant coating material. Raman spectroscopy is done to determine the coating capability of MoS2 on graphene. Surface morphology of our MoS2/graphene heterostructure is characterized by using optical microscopy, scanning electron microscopy, and atomic force microscopy. In addition, density functional theory-based calculations are performed to understand the energy barrier performance of MoS2 against nitrogenation. The penetration of nitrogen atoms through a defect-free MoS2 layer is prevented by a very high vertical diffusion barrier, indicating that MoS2 can serve as a protective layer for the nitrogenation of graphene. Our experimental and theoretical results show that MoS2 material can be used both as an efficient nanocoating material and as a nanoscale mask for selective nitrogenation of graphene layer.TUBITAK (116C073); The Science Academy, Turkey, under the BAGEP program; National Science Foundation USA NSF DMR-155222

Theoretical and experimental investigation of conjugation of 1,6-hexanedithiol on MoS2

We report an experimental and theoretical investigation of conjugation of 1,6-Hexaneditihiol (HDT) on MoS2 which is prepared by mixing MoS2 structure and HDT molecules in proper solvent. Raman spectra and the calculated phonon bands reveal that the HDT molecules bind covalently to MoS2. Surface morphology of MoS2/HDT structure is changed upon conjugation of HDT on MoS2 and characterized by using Scanning Electron Microscope (SEM). Density Functional Theory (DFT) based calculations show that HOMO-LUMO band gap of HDT is altered after the conjugation and two-S binding (handle-like) configuration is energetically most favorable among three different structures. This study displays that the facile thiol functionalization process of MoS2 is promising strategy for obtaining solution processable MoS2.TUBITAK (116C073); The Science Academy, Turkey under the BAGEP progra

Effect of Molecular Architecture on Cell Interactions and Stealth Properties of PEG

PEGylation, covalent attachment of PEG to therapeutic biomolecules, in which suboptimal pharmacokinetic profiles limiting their therapeutic utility are of concern, is a widely applied technology. However, this technology has been challenged by reduced bioactivity of biomolecules upon PEGylation and immunogenicity of PEG triggering immune response and abrogating clinical efficacy, which collectively necessitate development of stealth polymer alternatives. Here we demonstrate that comb-shape poly­[oligo­(ethylene glycol) methyl ether methacrylate] (POEGMA), a stealth polymer alternative, has a more compact structure than PEG and self-organize into nanoparticles in a molecular weight dependent manner. Most notably, we show that comb-shape POEGMA promotes significantly higher cellular uptake and exhibits less steric hindrance imposed on the conjugated biomolecule than PEG. Collectively, comb-shape POEGMA offers a versatile alternative to PEG for stealth polymer–biomolecule conjugation applications

A novel model approach for esophageal burns in rats: a comparison of three methods

WOS: 000356981000004PubMed: 23456816Background: Corrosive esophageal injury causes serious clinical problems. We aimed to create a new experimental esophageal burn model using a single catheter without a surgical procedure. Materials and methods: We conducted the study with two groups of 12 male rats that fasted for 12 h before application. A modified Foley balloon catheter was inserted into the esophageal lumen. the control group was given 0.9% sodium chloride, while the experimental group was given 37.5% sodium hydroxide with the other part of the catheter. After 60s, esophagus was washed with distilled water. the killed rats were examined using histopathological methods after 28 days. Results: in comparison with the histopathological changes experienced by the study groups, the control groups were observed to have no pathological changes. Basal cell degeneration, dermal edema, and a slight increase in the keratin layer and collagen density of submucosa due to stenosis were all observed in the group subjected to esophageal corrosion. Conclusion: A new burn model can thus, we believe, be created without the involvement of invasive laparoscopic surgery and general anesthesia. the burn in our experiment was formed in both the distal and proximal esophagus, as in other models; it can also be formed optionally in the entire esophagus