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ЛАБОРАТОРНАЯ МЕДИЦИНА
LABORATORY MEDICINE
УДК 54.01; 54.02; 54.05
*J.M. Jandosov1, 2, 3,A.zh. Baimenov2,3, a.t. Orazbekov3, E.M. Maral3, A.S. Nurkeev2, T.S. Nurgozhin1, Z.A. Mansurov23
1School of Pharmacy, Asfendiyarov Kazakh National Medical University, 94 Tole bi Street, Almaty, Kazakhstan 2lnstitute of Combustion Problems, 172 Bogenbay Batyr Street, Almaty, Kazakhstan 3Al-Farabi Kazakh National University, 71 Al-FarabiAvenue, Almaty, Kazakhstan Corresponding author E-mail: [email protected]
MORPHOSTRUCTURE OF MAGNETITE NANOPARTICLES SYNTHESIZED VIA GLYCOL
METHOD
Magnetic nanoparticles (MNP) were prepared by way of the glycol synthesis for the potential use in magnetic resonance imaging and the possibility of managing a local hyperthermia of a tumor as well as for vector drug delivery to target cells of the human body. Samples Fe3O4-EG, Fe3O4-TREG, Fe3O4-TMG were obtained by thermal decomposition (partial reduction) of Fe(AcAc)3 in ethylene glycol, triethylene glycol and tetramethylene glycol, respectively. The samples of Fe3O4 nanoparticles were investigated using modern physico-chemical methods: X-ray diffraction analysis (XRD), Scanning Electron Microscopy (SEM), and Transmission Electron Microscopy (TEM).
Keywords: MAGNETIC NANOPARTICLES, GLYCOL METHOD, PARTICLE SIZE DISTRIBUTION, AGGREGATION, THERMAL DECOMPOSITION, SUPERPARAMAGNETISM
1. INTRODUCTION
Nanoparticles with magnetic properties are of significant interest for medicinal science, which is associated with the possibility of remote control of the particles and the derived structures when an external magnetic field is applied. Currently, a wide range of magnetic nanoparticles (MNPs) based on metals has been synthesized: Co, Fe, Ni, iron oxides, ferrites MgFe2O4, СoFe2O4, MnFe2O4, LiFesOs, and alsotaPt, FePt, MnAl, SmCos, Fei4Nd2B etc.[1,2] Oxide nanoparticles have weaker magnetic properties than metal-based nanoparticles, but they are more resistant to oxidation. Nanosized iron oxide particles are of the most widely used in current biomedicine due to their low toxicity and stability of ferromagnetic and superparamagnetic characteristics [3, 4]. The magnetic nanoparticles studied in this communication were obtained using the glycol synthesis, which undergoes via partial reduction of iron (III) acetylacetonate in a polar medium of a variety of glycols: ethylene glycol (EG), triethylene glycol(TREG) and tetramethylene glycol (TMG). Glycols in the technique applied are used in order to reduce iron (III) acetylacetonate (Fe(AcAc)3) to magnetite (iron (II, III) oxide or Fe3O4), as well as to stabilize and control the nanoparticles growth and also to inhibit interparticle aggregation. Stabilization of magnetite nanoparticles is realized due to the interaction of functional hydroxyl groups of glycols with the nanoparticles surface leading to the formation of chelate complexes, where the interaction of two hydroxyl groups of a glycol (diol) fragment with the surface of Fe3O4speciestakes place [5, 6]. At the same time the resistance against the aggregation of the obtained magnetic nanoparticles due to interparticle interactions occurs herein.
Further surface functionalization of the magnetic Fe3O4 nanoparticles to be used as contrast agents in MRI may make it possible to control local tumor hyperthermia, as
well as vector-mediated drug delivery to the target tumor cells. Such nanoparticles are hydrophilic and readily to be dispersed in water and biological fluids, probably due to the adsorption of glycol molecules on their surface. The morphostructure, as well as the major characteristics of the obtained nanomaterials were assessed using the following physicochemical methods of analysis: XRD, SEM and TEM.
2. EXPERIMENTAL
2.1. Methods for preparation of Fe3O4 nanoparticles in various glycols
Weighed portions of iron (III) acetylacetonate: 3.53 g in the case of EG, 3.95 g in the case of TREG and TMG were dissolved in 140 ml of the corresponding glycol in a three-necked flask equipped with a reflux condenser, a capillary tube for supplying argon, and a thermometer. The solutions were heated to 180°C and maintained for 3 hours (in the case of EG), 30 minutes (in the case of TREG and TMG), respectively. In the case of EG (boiling points (b.p).: 180° C), the solution was distilled off until the glycol was completely evaporated, the precipitate was washed with ethanol (3 x 50 ml) and dried at 250° C in inert atmosphere. In the case of the use of TREG and TMG, the solutions of iron (III) acetylacetonate were heated toa corresponding b.p: 280°C for TREG, 224°C for TMG and maintained for another 30 minutes; after cooling to room temperature, the homogeneous black colloidal suspension was diluted with 56 ml of ethanol. MNPs were precipitated by the addition of 112 ml of ethyl acetate (99.8%). The precipitate was separated using a magnet, together with decantation of the supernatant liquid. In order to remove excess of glycol from MNPs, the precipitate was redispersed in 56 ml in an ultrasonic bath, and the dispersion was precipitated with 112 ml of ethyl acetate. The dispergation/sedimentation procedure was repeated three times. The washed product was dried in an oven at
80 ° C for 1 h in inert athmosphere. An experimental setup for the synthesis of Fe3O4-TREG magnetic nanoparticles sample is displayed in Figure 1. 2.2 Physicochemical methods of investigation
2.2.1 X-ray phase analysis (XRF)
X-ray diffraction patterns of the samples were obtained on a DRON-3M diffractometer using cobalt and copper radiation in digital form. Sample shooting mode: the voltage in the X-ray tube is 30 kV at a current of 30 mA. The scanning step size is 20 = 0.05o, the information time point at the step size is 1.0 second. During the scanning, the sample was rotated in its plane at rate of 60 rpm. Preliminary processing of X-ray diffraction patterns to determine the angular position and the intensities value was carried out using the "Fpeak" program. The phase analysis was performed using the PCPDFWIN program supplemented with a PDF-2 diffractometric database.
2.2.2 Scanning electron microscopy (SEM/EDS).
The morphology of the samples was investigated using a QUANTA 3D 200i microscope (FEI, USA) with an accelerating voltage of 30 kV. For local analysis of a sample chemical composition, the microscope is equipped with an EDS energy dispersive X-ray spectrometer, equipped with a semiconductor detector with an energy resolution of 128 eV resolution (polymer, window d=0.3 mm) and a focused electron beam.
2.2.3 Transmission electron microscopy (TEM).
The morphological features and nanoparticles sizes were assessed using TEM device (electron microscope JEM 1011, JEOL, Japan) with a resolution of up to 0.3 nm, with an accelerating voltage of 100 kV. The samples were dispersed in bidistilled water, then applied to standard collodion-coated copper grids, the grids were placed in a holder, which was inserted into the electron microscope chamber.
3. RESULTS AND DISCUSSION
Figure 1 - Experimental setup for the synthesis of Fe3O4-TREG magnetic nanoparticles
X-ray diffraction patterns of Fe3O4-EG, Fe3O4-TREG and Fe3O4-TMG samples were recorded on a DRON-3M diffractometer and are shown in Figure 2 (a-c). Comparative X-ray diffraction pattern [7] of a sample is shown in Figure 2 (d).
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Figure 2 - X-ray diffraction patterns of Fe3O4-EG (a) and Fe3O4-TREG (b) Fe3O4-TMG (c) and a comparative sample X-ray diffraction pattern [7] (d)
From the presented X-ray diffraction patterns shown in Figure 2 (a-c), it follows that the samples of magnetite nanoparticles are represented by magnetite monophase with a cubic spinel structure. Using the "Win Fit" program, the average crystallite sizes were calculated according to the Scherrer equation:
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width of the diffraction reflection at half maximum of the peak intensity, normalized for the instrumental component;^ - instrumental broadening;^ - analytical broadening.
According to the calculation, the average crystallite sizes amount to6.2 nm forFe3O4-EG, 10.5 nm for Fe3O4-TREG, while 10.5 nm for Fe3O4-TMG, respectively. Apparently, the samples are represented by magnetite monophase.The morphology and structure (sizewise speaking) of the Fe3O4-EG sample particles were determined by scanning electron microscopy.SEM-images of Fe3O4-EG sample are shown in Figure 3.
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Figure 3- SEM-images of Fe3O4-EG sample at magnification: (a) x 10000; (b) x 50000; (c) a comparative sample image [7].
From Figure 3(a, b)it follows, that nanoparticles are aggregated into spheroidal (snowball-like) microstructures with an average size of 2.2 |m, which have magnetic properties. Figure 3c displays an image of a crystalline product, e.g.: iron (III) alkoxide obtained according to a similar method [7], which, by contrast, does not exhibit magnetic properties.
The morphology, dispersity, and average size of Fe3O4-TREG and Fe3O4-TMG magnetite nanoparticles samples were determined using transmission electron microscopy. High-resolution TEM-images of nanoparticles of Fe3O4-TREG and Fe3O4-TMG samples are shown in Figure 4.
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Figure 4 - TEM-images of FeaO4-TREG (a, b) and FeaO4-TMG (c, d) samples with magnification: (a) x 120000; (b) x 300000;
(c) x 120000; (d) x 300000, respectively
According to TEM data, the dispersions of Fe3O4-TREG magnetite nanoparticles tend to form agglomerates consisting of various spherical particles of a size ranging within 25-50 nm. Particles of the Fe3O4-TMG sample form agglomerates of a size variation from 20 to 100 nm. Yet the average nanoparticle size for both samples Fe3O4-TREG and Fe3O4-TMG amounts to 6 ± 3 nm.
samples consist of magnetite monophase. Hence, the methods employed in this study make it possible to synthesize ferrous superparamagnetic nanoparticles with a narrow size distribution being optimal in the terms of monodispersity,it is especially effective when triethylene glycol is used.
CONCLUSION
The syntheses of magnetite nanoparticles (Fe3Û4) from iron (III) acetylacetonate (Fe(AcAc)3) in various glycols (ethylene glycol, triethylene glycol and tetramethylene glycol) were carried out.
It is shown that in the course of Fe(AcAc)3 thermal decomposition due to the partial reduction of Fe3+ions to Fe2+, magnetite nanoparticles, i.e.: an iron oxide (FeO/Fe2O3) are formed using glycols. Hence, according to SEM data, in the Fe3O4-EG sample synthesized in ethylene glycol, the particles are aggregated into snowball-like spherical microstructures with sizes of ca. 15 ^m. However, according to the XRD data, the average crystallite size is ca. 6.2 nm. According to the TEM data, of the nanoparticles sizes of Fe3O4-TREG and Fe3O4-TMG samples synthesized in triethylene glycol and tetramethylene glycol, respectively, are ranged within 3-10 nm. In this regard, the nanoparticles of the Fe3O4-TREG sample are less aggregated compared to the nanoparticles of the Fe3O4-TMG sample. According to XRD data, the average crystallite size in both samples is ca. 10.5 nm, and all three
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5 Wan S., Huang J., Yan H., Liu K. Size-controlled preparation of magnetite nanoparticles in the presence of graft copolymers //Journal of Materials Chemistry. - 2006- Vol. 16. - P. 298-303.
6 Wan S., Zheng Y., Liu Y., Yan H., Liu K. Fe3O4 Nanoparticles coated with homopolymers of glycerol mono(meth)acrylate and their block copolymers. // Journal of Materials Chemistry. - 2005 - Vol. 15.Vol.-P.3424-3430.
7 WeiCai, Jiaqi Wan. Facile synthesis of superparamagnetic magnetite nanoparticles in liquid polyols// Journal of Colloid and Interface Science. - 2007 -Vol. 305. - P. 366-370.
8 Khlebnikov V.K., Vishvasrao KH.M., Sokol'skaya M.A., Kabanov A.V. Vodorastvorimyye magnitnyye nanochastitsy kak potentsial'nyye agenty dlya magnitnoy gipertermii// Vestnik MITKHT, - 2012, - T. 7, № 1. - S. 66-70.
*Ж. M. ЖАНДОСОВ1, 2 3, А. Ж. БАЙМЕНОВ2, 3, А. Т. ОРАЗБЕКОВ3, E.M. МАРАЛ3, А С. НУРКЕЕВ2, Т.С. НУРГОЖИН1, З. А. MAНСУРОВ2, 3
ШколаФармации, Казахский Национальный Медицинский Университет им Асфендиярова, Алматы, Казахстан
2Институт Проблем Горения, Алматы, Казахстан 3Казахский Национальный Университет им аль-Фараби, Алматы, Казахстан
МОРФОСТРУКТУРА НАНОЧАСТИЦ МАГНИТИТА СИНТЕЗИРОВАННЫХ ГЛИКОЛЬНЫМ МЕТОДОМ
Резюме: Монодисперсные магнитные наночастицы (МНЧ) были получены гликольным методом для дальнейшего потенциального использования в магнитно-резонансных исследованиях и возможности управления локальной гипертермии опухоли, а также для векторной доставки лекарственных препаратов к клеткам-мишеням организма человека. Образцы Гвз04-ЭГ, Гвз04-ТРЭГ и Гвз04-ТМГбыли синтезированы путем термического разложения (частичного восстановления) ¥г(АсАс)з в этиленгликоле, триэтиленгликоле и
тетраметиленгликоле, соответственно. Образцы наночастиц Гвз04 были исследованы с помощью современных физико-химических методов анализа: рентгенофазовый анализ (РФА), сканирующая электронная микроскопия (СЭМ) и просвечивающая электронная микроскопия (ПЭМ).
Ключевые слова: МАГНИТНЫЕ НАНОЧАСТИЦЫ, ГЛИКОЛЬНЫЙ МЕТОД, РАСПРЕДЕЛЕНИЕ ЧАСТИЦ ПО РАЗМЕРАМ, АГРЕГАЦИЯ, ТЕРМИЧЕСКОЕ РАЗЛОЖЕНИЕ, СУПЕРПАРАМАГНЕТИЗМ
*Ж. M. ЖАНДОСОВ1, 2, 3, A. Ж. БАЙМЕНОВ2, 3, A. T. ОРАЗБЕКОВ3, E. M. МАРАЛ3, A. С. НУРКЕЕВ2, T. С. НУРГОЖИН1, З. A. MAНСУРОВ2, 3
1Асфендияров атындагы Казац улттыцмедициналыцуниверситету Фармация мектебу Алматы, Казахстан Жану проблемалары институты, Алматы, Казахстан 3эл-Фараби атындагы Казац улттыцуниверситету Алматы, Казахстан
ГЛИКОЛ ЭД1С1МЕН СИНТЕЗДЕЛГЕН МАГНЕТИКАЛЬЩ НАНОБ6ЛШЕКТЕРДЩ МОРФО;¥РЫЛЫМЫ
Туши: Монодuсперстiмагниттжнанобвлшектер (MNP) гликоль эдiсiмен магнитт^резонанстыц зерттеулерде эрi царай жергiлiктi ск гипертермиясын бацылау мумктдтн потенциалды цолдану ушш, сондайац дэрь дэрмектердi адам агзасыныц мацсатты жасушаларына жетюзу ушт алынган. Fe3Ü4-EG, Fe3Ü4-TREG жэне Fe3Ü4-TMG yлгiлерi Fe(AcAc)3 термиялыц ыдырату (шмара цалпына келтiру) арцылы сэйкестше этиленгликоль, триэтиленгликоль жэне
тетраметиленгликолда синтезделдь Fe3Ü4
нанобвлшектершщ yлгiлерi заманауи физико-химиялыц талдау эдктерт цолдана отырып зерттелдг. рентгендкфазалыц талдау (РФТ), сканерлейтн электронды микроскопия (СЭМ) жэне трансмиссиялыц электронды микроскопия (ТЭМ).
TyüiHdi свздер: МАГНИТТ1К НАНОБвЛШЕКТЕР, ГЛИКОЛЬ ЭД1С1, Б6ЛШЕКТЕРДЩ YЛЕСТlРlЛУl, АГРЕГАЦИЯ, ТЕРМИЯЛЫК ЫДЫРАУ,
СУПЕРПАРАМАГНЕТИЗМ
