Role of iron oxide core of polymeric nanoparticles in the thermosensitivity of colon cancer cell line HT-29

Purpose: In this study the effect of PLGA polymeric nanoparticles as a 5-fluorouracil (5-FU) carrier with and without iron oxide core and hyperthermia were investigated on the level of DNA damage in a spheroid culture model of HT-29 colon cancer cell lines by alkaline comet assay.Materials and methods: First, HT-29 colon cancer cells were cultured in vitro as spheroids with a mean diameter of 100 μm. The spheroids were then treated with different concentrations of 5-FU or nanoparticles as 5-FU carriers with and without an iron oxide core for one volume-doubling time of the spheroids (71 h) and hyperthermia at 43 °C for 1 h. Finally, the effect of treatment on viability and level of DNA damage was examined using trypan blue dye exclusion assay and alkaline comet assay, respectively.Results: Results showed that hyperthermia in combination with 5-FU or nanoparticles as 5-FU carriers significantly induced the most DNA damage as compared with the control group. The extent of DNA damage following treatment with 5-FU-loaded nanoparticles combined with hyperthermia was significantly more than for 5-FU combined with hyperthermia. In comparison to the effect of 5-FU-loaded nanoparticles with the iron oxide core and 5-FU-loaded nanoparticle without the iron oxide core, the nanoparticles with the iron oxide core combined with hyperthermia induced more DNA damage than the nanoparticles without the iron oxide core.Conclusions: According to this study, hyperthermia is a harmful agent and nanoparticles are effective delivery vehicles for drugs into colon cancer cells. The iron oxide filled nanoparticles increased the effect of the hyperthermia. All these factors have a significant role in the treatment of colorectal cancer cells. © 2015 Informa UK Ltd. All rights reserved

In vivo evaluation of the combination effect of near-infrared laser and 5-fluorouracil-loaded PLGA-coated magnetite nanographene oxide

Magnetite nanographene oxide has exhibited great potential in drug delivery and photothermal therapy (PTT) for cancer treatment. Here we developed 5-fluorouracil-loaded poly (lactic-co-glycolic acid)-coated magnetite nanographene oxide (NGO-SPION-PLGA-5-Fu) to simplify combined PTT and chemotherapy in one complex. The nanocarrier was synthesized using a modified O1/W1/O2/W2 multiple emulsion solvent evaporation method and was characterized for size, zeta potential, drug loading, in vitro and in vivo release. In this paper, in vivo suppression effect of PTT and chemotherapy using this synthesized magnetite nanographene oxide was studied. The in vitro release of 5-Fu from nanoparticles showed that 41.36 of the drug was released within 24�h. In vivo release showed that 5-Fu has a sustained release profile and prolonged lifetime in the rabbit plasma. Remarkably, a single injection of NGO-SPION-PLGA-5-Fu and 808�nm near-infrared laser (NIR) irradiation for 3�min effectively suppressed the growth of tumours compared with 5-Fu alone (p�<�.01). Magnetic resonance imaging (MRI) confirmed that the magnetic nanographene oxide was effectively targeted to the tumour site. Therefore, NGO-SPION-PLGA-5-Fu showed excellent PTT efficacy, magnetic targeting property, and MRI ability, indicating that there is a great potential of NGO-SPION-PLGA-5-Fu for cancer theranostic applications. © 2018 Informa UK Limited, trading as Taylor & Francis Grou

Effects of ultrasound irradiation on the release profile of 5-fluorouracil from magnetic polylactic co-glycolic acid nanocapsules

Background: Drug nano-carriers are one of the most important tools for targeted cancer therapy so that undesired side effects of chemotherapy drugs are minimized. In this area, the use of ultrasound can be helpful in controlling drug release from nanoparticles to achieve higher treatment efficiency. Objective: Here, we studies the effects of ultrasound irradiation on the release profile of 5-fluorouracil (5-Fu) loaded magnetic poly lactic co-glycolic acid (PLGA) nanocapsules. Methods: 5-Fu loaded magnetic PLGA nanocapsules were synthesized by multiple emulsification method. Particle size was measured by dynamic light scattering (DLS) and transmission electron microscope (TEM). The pattern of drug release was assessed with and without 3 MHz ultrasound waves at intensities of 0.3, 0.5 and 1 w/ cm2 for exposure time of 5 and 10 min in phosphate-buffered saline (PBS). Results: The size of nanoparticles was about 70 nm. Electron microscope images revealed the spherical shape of nanoparticles. The results demonstrated that the intensity and exposure time of ultrasound irradiation have significant effects on the profile of drug release from nanoparticles. Conclusion: It may be concluded that the application of ultrasound to control the release profile of drug loaded nanocapsules would be a promising method to develop a controlled drug delivery strategy in cancer therapy. © 2016 Shiraz University of Medical Sciences. All rights reserved

Vc coating of steels in molten borax bath

Tez (Doktora)--İTÜ Fen Bil. Enst., 1992Türkiye'nin sahip olduğu en önemli yeraltı kaynakla rından biri bor rezervleridir. Bor ve türevlerinin en düstride kullanım alanları oldukça geniştir. Bor ve bor bileşiklerin kullanım alanlarına en iyi örnekler borlama ve karbürleme gibi termodifüzyonel işlemlerdir. îlk kez 1971 yılında Toyota firması tarafından geliştirilen TD (Toyota Difüzyon Prosesi) işlemi ile çeliklere üzerine değişik karbür tabakaları kaplanmıştır. Yüzeyi karbürlenmiş çelik grubu malzemeler, yüzeyin çok sert (sertliği yaklaşık 2000 kg/mm2), aşınmaya daya nıklı ve sürtünme katsayısının çok düşük olması sebebiy le endüstride birçok kullanım alanı bulmuştur. Karbürlü malzemelerin korozyona ve ergimiş alüminyuma karşı daya nımları oldukça yüksektir. Karbürlerle yüzey sertleştirme, esas olarak yüksek sıcaklıkta boraks içerisinde çözünen ferro-alaşımlarınm çeliğe yayınım olayıdır. Bu işlem genellikle 850-1200°C sıcaklık aralığında, iki ile altı saat süreler arasında bekletilmesiyle gerçekleşmektedir. Bu işlemin endüstri yel uygulamalarında yayınma potansiyeli yüksek olan kar bürleme ortamları gereklidir. Burada sunulan teze ait deneysel çalışmalarda, kar bürleme yöntemi olarak "Sıvı ortamda karbürleme" ve kar bürleme işleminin gerçekleştiği banyonun ana bileşeni olarak kristal su içermeyen boraks (^26407), ferro- vanadyum ve kalsine borik asit seçilmiştir. En uygun banyo bileşimini bulmak amacıyla çeşitli banyolar hazır lanmış ve çalışma koşulları gözönüne alındığında optimum banyo bileşiminin %85 boraks, %10 f erro-vanadyum, %5 kal sine borik asit olduğu belirlenmiştir. Sözü edilen banyo içerisinde 115 CrV 3 çeliği 940°C sıcaklığında yaklaşık altı saat bekletildiğinde çeliğin yüzeyinde 15jum kalınlı ğında bir VC tabakası oluşmaktadır. Çeşitli sıcaklık ve zamanlarda oluşturulan VC tabakasının fiziksel özellik leri, tabakanın oluşum kinetiği, kullanılan banyo aktif- liği incelenmiş ve bu banyo kullanılarak değişik çelik lerin karbürlenebilirliği ile bu çeliklerin içerisindeki çeşitli alaşım elementlerinin karbür tabakasına olan etkisi araştırılmıştır. Karbür kaplama yapılamayan az karbonlu çeliklerin sementasyonla yüzeyi karbonca zenginleştirilerek bilahe- re karbürlenebileceği görülmüştür. Bu proses ile toklu ğu geliştirilmiş olan sfero dökme demirlere de karbürle me yapılabileceği anlaşılmıştır.It is essential during the development of every country that efficient utilization of natural resources in favor of science, technology and mankind should be sought. Each year, substantial losses take place globally due to wear and corrosion. Corrosion only amount to about3.5 to 5% of the gross national product of a coun try. Annual corrosion cost of Turkey, alone amounts to about 4.5 Billion dollars for the year 1991. Such large losses concurrent with the industrial development have increased the demand for materials having high strength and stability. For this reason, recently ceramic materi als have received wide popularity. However, ceramic ma terials mainly due to their lack of ductility and tough ness behaviour, are more difficult to process than con ventional materials resulting in high costs during raw material preparation and shaping processes. For this reason, manufacturing of materials which are econom ically competative and which provide necessary struc tural and surface properties has become the primary focal point in recent years. Electrochemical, thermal, thermochemical, thermomechanical and gas phase depos ition methods are used widely to provide the required surface properties. The thermomechanical method is basically a process in which certain elements in solid, liquid and gas states diffuse into the material at high temperatures. By means of this method, carburizing, boronizing cement ation, nitriding and carbonitriding onto material sur faces are employed extensively. Carbides, unlike oxide or silicates, belong to a very special category of compounds since they are the first artifical refractories and exist in small quanti ties in nature. Because of their higher hardness values than other values and that they preserve these values up to about 500°C, carbides have found a large number of applicational fields in industry. Surface treatments are applied to metals in order to result in hard, abrasion and corrosion-resistant surfaces Although some of the surface treatment methods have been applied since past times, most have short history. The hard carbide layers must be thin enough to allow the elastic deformation of material and at the same time must be thick enough to prevent wear. vii Carburization is basically a thermomechanical process in which carbide forming elements diffuse into steel in a solid, gas or liquid medium. In solid state carburization Cr, Nb, V, Ta, Ti and Si carbides are coated on steels. The materials to be surface carburized are kept in a carbon containing powder at 950-1100°C temperatures for 10-30 hours. This method which is similar to pack carburization can be performed either in inert gas atmosphere or in an ambient atmosphere using tightly sealed containers. The composition for carbu rization comprises a carbide forming, a carbon contain ing compound having a boiling or sublimation point of 160° to 750°C, staying in solid state at room tempera ture, an activator and an inert filler. Mass % of the carburization composition: Carbide forming element % 40-70 Carbide containing compound % 0.5-215 Activator % 0.2-5 Inert filler The balance Inparalel with the development in vacuum technologies new progresses have taken place in gas phase deposition techniques such as CVD and PVD. The first studies for producing carbides and nitrides by CVD began in 1920. CVD coating of TiC, TiN and other carbides and nitrides were first performed by Van Arkel (1924) but prevention of metal and graphite inclusions from coated layers were too difficult. Thus problem has been solved by Meers (1931) by using metal chlorides and temperatures above 2000°C. Deposition of TiC and TiN on steels were first performed by Münster and Ruppert. CVD is generally defined as the deposition of a solid material onto a heated substrate surface as a result of chemical reactions in the gas phase. The proc ess operates at high temperatures above 500°C and under 10-760 Torr pressures. Conventional CVD is a process in which gaseous chemical reactants are transported to a reaction chamber under vacuum, activated thermally and made to react to form a solid deposit on the material. PVD (physical vapor deposition) similar to CVD is a process by which gas phase is deposited onto metal sub strates. TiC, TİN, A1203 and MoN coatings deposited by PVD process are applied to variety of materials. This process in used to deposit oxides, nixtrides and car bides on metals and alloys by gas heating or particle bombardment in a vacuum chamber. There are three kinds of PVD techniques operating between 400-450°C which are: i) Evaporation, ii) Ion plating, iii) Cathode Atomisation. viii The advantages of PVD over CVD can be stated as: - Possibility to operate at low temperatures, - Preservation of inherent properties arising from thermal treatments, - Lower residual stresses and distortion during cooling, - Ability to coat low melting temperatures materials, - Elimination of pollutants and effluents from the process, - Better quality and cost of deposits. Carburization in liquid bath is similar to normal salt bath heat treatment and necessitates single equip ments compared to CVD and PVD. Hardness and service life of component carburized with thus method are comparable to those produced by CVD and PVD, chlorides, fluorides, boron oxide and borax salts and V, Nb, Cr metallic pow ders or their ferroalloys can be used as the constituent of the liquid bath. Samples to be carburized are kept at 800-1200°C for 1-10 hours for carburization. Ulrich Baudis and his coworkers have carried out investigations on carburization by adding 1-30% vanadium or ferro- vanadium powders to a chloride and floride salt bath. Some of the compositions for carburizing iron group ma terials are as follows: a)-%90 BaC12 + %5 NaCl + %5 Pe-V b)-%87 BaCl2 + %13 Fe-V c)-%84 BaC12 + %9 NaCl + %7 Fe-V d)-%48 BaC12 + %24 KF + %7 NaF + %11 Fe-V Carburizing in molten borax bath (TD Process) has been researched and patented in Toyota Research Center by Arai and his co-workers in 1971. The TD process is an unique and a truly practical process in order to form dense, smooth and thin layers on a metal substrate. Car bides of mainly VC, NbC and Cr7C3 formed by TD process exhibit extreme hardness, high resistance to wear and oxidation. While immersing in a molten salt bath, a carbide layer grows on the extreme surface of a sub strate of a substrate material in the following steps: a) -Carbide forming elements dissolve into borax from the added compound, b) -Carbon atoms in the substrate surface combine with the CFB (Carbide Forming Elements) to produce a car bide layer, c) Growth of carbide layers are determined by the com position of material to be treated as well as process temperature and treatment time. VC, NbC and Cr-C hard carbide layers having differ ent crystal structure than that of substrate material form and grow on the material surface. The relation between layer thickness and time is determined as parab- ix olic which indicates a diffusion controlled process. Phase structures of carbide layers change with changing composition. The phases which accompany the layers di rectly effect the coating properties. For this reason, the compounds in the coated layers must be known. For example, because of its brittleness during heat treat ment V2C is an unwanted phase. Carbide layers have high hardness values. The Vickers hardness values are about 3200-3000 Vickers for VC, 2400-3100 Vickers for NbC and 1400-2000 Vickers for Cr-C. These hardness vaules are stable and fall slightly at high temperatures. TD Process provides significant benefits which can described as: - Saving of dies through die life improvement, - Saving of labor for die polishing, - Lubricant savings, - Reduction in labor for product finishing, - Reduction in die material cost and die fabrication cost, - Improvement in product quality due to improvement in surface roughness, appearance, dimensional precision. The advantages of TD process can be summarized as follows: - Simple equipment required, - Easy operations, - Selective carbide coating, - Low cost, - Uniform coating even on narrow recessed areas, - Good bath stability and life, - Easy removal of attached salt from the specimen, - Requires no protective atmosphere, - No air pollution, - Simultaneous core hardening. TD Process has entered various fields of Japanese automobile, chemical, textile and metallurgical indus tries. A great number of Japanese automobile makers and component makers including, Toyota group companies and their competitors. In addition to its widespread use in Japan, the process has spread to Australia, France, Italy, Taiwan, USA and UK. The fact that TD can produce the coatings with extreme properties only by using very cheap equipment is best suited for Turkey which has a substantial domestic market share in the automobile industry. This process has been originated and spearheaded by a private corpo ration. For this reason, the required complete knowhow regarding this practical technology could be very diffi cult. The aim in this investigation is to evaluate our understanding of the carbide coating process. For this purpose, DIN 115 CrV 3 steel was carburized in various bath compositions and the composition including borax + calcined boric acid + Pe-V was determined as the optimum bath. Thickness and homogeneity of the coated layers and fluidity of the bath were evaluated in deciding about the optimum bath. Phase structures of all heat treated specimens were detected by using a X-ray dif f Tactometer. In this investigation, VC layers were also formed by borax + Fe-V composition. However additions above 30% Pe-V decreased the fluidity and gave rise to problems in the removal of attached salt. Boric acid was added in order to increase the fluidity of the bath to minimize the amount of attached salt. Therefore considering the operation conditions, viscosity of bath, layer thickness and the attached salt to the specimen surface, 10-15% Fe-V + 5% calcined boric acid + borax was fixed as the optimum bath composition. Various range of layer thick ness values were obtained with 10% Fe-V + 85% borax + 5% calcined boric acid and 90% borax + 10% Fe-V bath compo sitions at 920-990°C temperatures for time periods of 2- 6 hours. Pore-free, dense strongly bonded and hard carbide layers were obtained. In addition, the study made on kinetics of carbide formation and activation of bath. The activation energy of carbon atoms to form carbide layers was found as «53 Kcal/mol. Carburizing in liquid bath is basically a process in which Fe-V dissolves in molten borax. But ferro alloys unlike metals are first oxidized. The solubility of oxides formed in borax bath is low. These oxides reach their maximum solubility with time. The factors affecting the maximum solubility are as follows: 1. Content of Pe-V in the bath, 2. Particle size of powders used, 3. Bath temperature, 4. Oxidation state of bath, 5. Agitation Carbide layers form as a result of oxidation of V coming from the added Fe-V powders. The oxidation state of V depends on the oxygen content, temperature of bath, kind of crucible and treatment time. Carbide formation was first proposed as a result of reaction between carbon atoms and solid ferro vanadium powders. But later it was found out that carbide form ing elements like vanadium oxidize and the oxides cause the formation of carbide layers. Therefore the rela tionship between temperature and standard energy values of vanadium oxides compounds have to be investigated. xi The most stable oxides of vanadium are VO and V2O3 since they have largest negative free energy of oxide formation. V2O5 is the unstable oxide of vanadium. Thermodynamic calculations predict that carbides can only be reduced by the carbon present in the system. Among different vanadium oxides, V2O5 has been deter mined to cause VC formation. The oxide which cause VC formation is reported as V2O3 in the literature on the basis of vanadium oxide formation per mole of V. However, stability of metallic oxides should have the basis of one mole of oxygen. Thus, it is apparent that V2O5 is less stable than V2O3. In addition to V2O5, free vana dium ions formed as a result of decreasing oxygen poten tial of the bath should also be considered for the car bide formation. The thickness of carbide layers has been found to increase with increasing carbon content for plain carbon steels using the bath proposed in this study. In the case of hot worked steels, increase in the Cr+Mo alloy content decreases the thickness of the carbide layers. The carbide layer thickness is relatively high for cold worked, high chromium and high carbon containing steels. But Cr presence decreased the carbide layer thickness in plain carbon steels. In summary, the following conclusions can be summa rized: i) Optimum bath composition for vanadium carbide coating is 85% borax + 10% f errovanadium (comprising 74% V) 5% calcined boric acid, ii) The amount of f errovanadium in the bath is not critical whereas bath viscosity plays an important role, iii) Approximately 5% calcined boric acid contributes to bath in practice whereas exceeding amounts affect the bath negatively, iv) Heat treatment temperatures must be above A3 steel temperature, v) unstable vanadium oxides occur in the active bath, vi) Carburization process is controlled by carbon atom diffusion in the steel, vii) optimum materials for coating are high carbon steels which do not have alloying elements, viii) Vanadium carbide coating has been also proved to take place in stainless steel pots by means of controlling the activity of the bath.DoktoraPh.D

Polymer-grafted superparamagnetic iron oxide nanoparticles as a potential stable system for magnetic resonance imaging and doxorubicin delivery

Currently, there is high interest in developing multifunctional theranostic platforms with both imaging and therapeutic functions. Herein, we report a facile approach to develop polymer-grafted superparamagnetic iron oxide nanoparticles (SPIONs) as a promising system for imaging and drug delivery. A random copolymer composed of pendant-activated ester moieties, that is, pentafluorophenyl acrylate (PFPA) and polyethylene glycol monomethyl ether methacrylate (PEGMA), were synthesized and grafted on SPION surfaces using the click reaction. The resultant multifunctional SPIONs were characterized using FT-IR, XRD, XPS, TGA and TEM, proving the presence of polymers on their surfaces. The formed polymer-grafted SPIONs are water-dispersible, stable, and biocompatible as confirmed by a cell viability assay. Relaxivity measurements show that they have a relaxivity of 134.40 mM-1 S-1, which is higher than the value obtained from the commercial FDA approved MRI contrast agent Ferumoxytol (85 mM-1 S-1). Furthermore, doxorubicin (DOX) was loaded onto the polymeric shell of modified SPIONs and exhibited fast drug release in response to acidic conditions (pH 5.4). These results clearly indicate that the prepared modified SPIONs have great potential to serve as a multifunctional nanosystem for T2-weighted MR imaging and therapy

Polymer-grafted superparamagnetic iron oxide nanoparticles as a potential stable system for magnetic resonance imaging and doxorubicin delivery

Currently, there is high interest in developing multifunctional theranostic platforms with both imaging and therapeutic functions. Herein, we report a facile approach to develop polymer-grafted superparamagnetic iron oxide nanoparticles (SPIONs) as a promising system for imaging and drug delivery. A random copolymer composed of pendant-activated ester moieties, that is, pentafluorophenyl acrylate (PFPA) and polyethylene glycol monomethyl ether methacrylate (PEGMA), were synthesized and grafted on SPION surfaces using the click reaction. The resultant multifunctional SPIONs were characterized using FT-IR, XRD, XPS, TGA and TEM, proving the presence of polymers on their surfaces. The formed polymer-grafted SPIONs are water-dispersible, stable, and biocompatible as confirmed by a cell viability assay. Relaxivity measurements show that they have a relaxivity of 134.40 mM-1 S-1, which is higher than the value obtained from the commercial FDA approved MRI contrast agent Ferumoxytol (85 mM-1 S-1). Furthermore, doxorubicin (DOX) was loaded onto the polymeric shell of modified SPIONs and exhibited fast drug release in response to acidic conditions (pH 5.4). These results clearly indicate that the prepared modified SPIONs have great potential to serve as a multifunctional nanosystem for T2-weighted MR imaging and therapy

Evaluation of the combined effect of NIR laser and ionizing radiation on cellular damages induced by IUdR-loaded PLGA-coated Nano-graphene oxide

Glioma is one of the most common malignant cancers of the central nervous system (CNS). Radiatherapy and chemotherapy may be used to slow the growth of tumors that cannot be removed with surgery. The current study developed a combination therapy tool using Nanographene oxide (NGO) functionalized with poly lactic-co-glycolic acid (PLGA) as a carrier of 5-iodo-2-deoxyuridine (IUdR) for glioma cancer treatment. U87MG cells were treated in different groups with IUdR, PLGA-coated Nanographene oxide (PLGA-NGO), IUdR-loaded PLGA-coated Nanographene oxide (IUdR-PLGA-NGO), 2 Gy 6 MV X-ray radiation, and near-infrared region (NIR) laser radiation. PLGA-NGO showed excellent biocompatibility, high storage capacity for IUdR and high photothermal conversion efficiency. It was effectively employed to create cell damage in the U87MG cell line in the presence of X-ray (6 MV) and NIR laser. Moreover, IUdR-PLGA-NGO + X-ray + NIR laser significantly reduced the plating efficiency of the cells in comparison with IUdR-PLGA-NGO + X-ray and IUdR-PLGA-NGO + NIR laser. Furthermore, Prussian blue staining showed that IUdR-PLGA-NGO-SPIONs were delivered into glioblastoma cells. The PLGA-NGO loaded with IUdR under NIR and X-ray radiation exhibited the highest cytotoxicity toward U87MG cells when compared with other treatment methods, indicating efficient radio-photothermal targeted therapy. © 2017 Elsevier B.V

Tri-block copolymer nanoparticles modified with folic acid for temozolomide delivery in glioblastoma

In the present study, Folic Acid (FA) ligand was used to functionalize Temozolomide-loaded Poly (ethylene Glycol)�Poly (Butylene Adipate)�Poly (ethylene Glycol)-coated magnetite nanoparticles (TMZ-SPION-PEG-PBA-PEG) for targeted chemotherapy of glioma cells. Four types of nanoparticles were synthesized with the hydrodynamic diameters of 24�49 nm. Using MTT, Prussian blue, and ICP-OES assays, the cytotoxicity effect and cellular uptake of nanoparticles were evaluated in C6 cancer cells and OLN-93 normal cells. Moreover, in vitro anti-tumor efficacy of nanoparticles was evaluated through colony formation, quantitative real-time PCR, and flow cytometry analysis. As compared to OLN-93 cells TMZ-SPION-PEG-PBA-PEG-FA nanoparticles showed an increase in the cytotoxicity of the loaded TMZ in C6 cells within 24 and 48 h treatment (P < 0.0001), while such effect was not observed in the case of non-targeting nanoparticles. The colony formation, flow cytometry, and real-time PCR assays showed that TMZ-SPION-PEG-PBA-PEG-FA led to the enhancement of inhibitory effects to C6 cells compared to TMZ alone (P < 0.05). These results suggested that TMZ-SPION-PEG-PBA-PEG-FA could effectively slow down cell proliferation, due to the targeting effect and the high accumulation of TMZ in C6 cells via an FA-receptor mediated endocytosis. In conclusion, TMZ-loaded magnetite FA-conjugated PEG-PBA-PEG NPs could be used as a targeted drug delivery system for targeted therapy of brain glioma. © 2019 Elsevier Lt