Microemulsion Synthesis of Nanoparticles

U ovom pregledu prikazane su mikroemulzijske tehnike za sintezu metalnih, metal-oksidnih, sulfidnih i polimernih nanočestica. Sinteza se izvodi u mikroemulzijama voda-u-ulju, miješanjem dviju mikroemulzija, od kojih jedna sadrži kationski prekursor, a druga precipitacijski medij ili redukcijsko sredstvo. Nanočestice metala dobivaju se redukcijom metalnog kationa s jakim redukcijskim sredstvima uz oslobađanje vodika prikladnim redukcijskim sredstvom. Na sličan način mogu se pripraviti i nanočestice legura od soli različitih metala pod uvjetom da se metali međusobno miješaju. Mikroemulzijska tehnika veoma je pogodna i za nanošenje nanočestica na različite podloge. Na taj način mogu se dobiti visokoaktivni katalizatori od nanočestica Pt, Pd, Rh i drugih plemenitih metala. Metalni oksidi i hidroksidi pripravljaju se hidrolizom ili taloženjem u vodenoj jezgri mikroemulzije. Da se spriječi oksidacija nanočestica, osobito Fe, čestice se prevlače inertnim metalima, oksidima, različitim polimerima i dr. Prevlačenjem se može postići dodatna funkcionalnost; npr. prevlačenje zlatom omogućava naknadnu funkcionalizaciju organskim spojevima koji sadrže sumpor, zahvaljujući jakoj tiolnoj vezi Au–S. Polimerne prevlake smanjuju toksičnost nanočestica i povećavaju biokompatibilnost, a funkcionalne skupine na površini omogućavaju razne primjene u biomedicini. Reakcije polimerizacije ili umrežavanja mogu se inicirati u vodenim jezgrama mikroagregata kemijskim sredstvima ili npr. UV ili ionizirajućim zračenjem. Prednosti mikroemulzijske polimerizacije su velika brzina, jednolična veličina čestica, stabilnost te visoki stupanj polimerizacije. Nanočestice magnetita pobuđuju velik interes zbog primjene u biomedicini. Magnetit je biokompatibilni materijal, a može se pripremiti u obliku dobro dispergiranih nanočestica manjih od 4 nm, koje imunosni sustav ne prepoznaje. Prikazana je vlastita metoda mikroemulzijske sinteze nanočestica magnetita potpomognuta γ-zračenjem.Nanoparticles and nanomaterials have wide applications in electronics, physics, material design, being also utilized as sensors, catalysts, and more and more in biomedicine. Microemulsions are an exceptionally suitable medium for the synthesis of nanoparticles due to their thermodynamical stability, great solubility of both polar and nonpolar components, as well as their ability to control the size, dispersity and shape of the particles. This review presents microemulsion techniques for the synthesis of inorganic nanoparticles. It takes place in water-in-oil microemulsions by mixing one microemulsion with a cationic precursor, and the other with a precipitating or reducing agent, or by direct addition of reducing agents or gas (O2, NH3 ili CO2 ) into microemul sion (Fig. 1). Metal nanoparticles are used as catalysts, sensors, ferrofluids etc. They are produced by reducing the metal cation with a suitable reducing agent. In a similar way, one can prepare nanoparticles of alloys from the metal salts, provided that the metals are mutually soluble. The microemulsion technique is also suitable for depositing nanoparticles onto various surfaces. Highly active catalysts made from nanoparticles of Pt, Pd, Rh and other noble metals may be obtained in this way. Metal oxides and hydroxides may be prepared by hydrolysis or precipitation in the water core of microemulsion. Precipitation can be initiated by adding the base or precipitating agent into the microemulsion with water solution of metal ions. Similarly, nanoparticles may be prepared of sulphides, halogenides, cyanides, carbonates, sulphates and other insoluble metal salts. To prevent oxidation of nanoparticles, especially Fe, the particles are coated with inert metals, oxides, various polymers etc. Coating may provide additional functionality; e.g. coating with gold allows subsequent functionalization with organic compounds containing sulphur, due to the strong Au–S bond. Polymer coatings decrease toxicity of the nanoparticles and increase their biocompatibility, and the functional groups on the surface enable specific applications in biomedicine. Microemulsion synthesis is convenient both for organic and polymer particles. Polymerization or crosslinking reactions may be initiated in the water core of microaggregates by using chemicals, UV or ionizing radiation (Fig. 3). Microemulsion polymerization is advantageous due to fast reactions, uniform particle size, great stability and high polymerization degree. Magnetite nanoparticles induce great interest due to biomedical applications. Magnetite is a biocompatible material that may be prepared in the form of well-dispersed nanoparticles smaller than 4 nm, which are not recognized by the immune system. The authors’ own approach for the synthesis of magnetite nanoparticles using γ-irradiation assisted microemulsion technique is described (Figs. 5–10)

Introduction to Microemulsions

U pregledu su prikazane glavne karakteristike mikroemulzija i njihove primjene. Mikroemulzije su termodinamički stabilni i optički izotropni sustavi koji se sastoje od ulja, vode i amfifilnih molekula koje nazivamo surfaktantima i kosurfaktantima. Mikroemulzija može biti sastavljena od mikrokapljica ulja u vodi ili od mikrokapljica vode u ulju, ili može biti tzv. bikontinuirana faza u kojoj se voda i ulje kontinuirano isprepliću u strukturi nalik spužvi. Mikroemulzije su samoorganizirajući sustavi i nastaju bez utroška energije. Mikroemulzije voda-u-ulju važne su za sintezu raznih anorganskih materijala. Reakcije se zbivaju u malom obujmu vode unutar mikrokapljice i zbog toga produkti često imaju poboljšane karakteristike u pogledu čistoće i raspodjele čestica po veličini. Veličinu mikrokapljica moguće je kontrolirati vrstom i omjerom surfaktanta i kosurfaktanta te kemijskim sastavom uljne i vodene faze. Mikroemulzije mogu imati složeno fazno ponašanje, koje se obično prikazuje faznim dijagramom. Osim spomenutih čistih strukturnih tipova, u mikroemulziji može biti zastupljeno i više njih odjednom. Surfaktanti su amfifilne molekule građene od hidrofilne glave i lipofilnog repa, zbog čega imaju afinitet i prema vodi i prema ulju. Njihova glavna svojstva su adsorpcija na međupovršini i samoorganizacija u supramolekulske strukture. Stvaranjem sloja na granici faza surfaktanti smanjuju površinsku napetost i stabiliziraju mikroemulziju. Prema vrsti hidrofilnog dijela surfaktanti se dijele u anionske, kationske, neionske i amfoterne. U pregledu su prikazane kemijske strukture njihovih tipičnih predstavnika. Mikroemulzijski agregati mogu imati različit oblik, kao npr. sferičan, elipsoidan, cilindričan, crvolik ili dvoslojni. Bikontinuirana faza također se javlja u više različitih oblika, npr. u heksagonskom, lamelnom ili kubičnom. Glavni parametri koji određuju mikrostrukturu su zakrivljenost međupovršinskog filma i kritični parametar pakiranja.Hoar and Schulman were the first (in 1943) to describe the transparent water-in-oil dispersion. They noted that a certain combination of water, oil, surfactant and alcohol cosurfactant would produce a clear homogeneous "solution", which Schulman in 1959 termed microemulsion. Schulman’s model of the inverse submicroscopic micelle is shown in Fig. 1. The IUPAC definition describes microemulsion as a dispersion made of water, oil, and surfactant(s), which is an isotropic and thermodynamically stable system with dispersed domain diameter varying approximately from 1 to 100 nm, usually 10 to 50 nm. Water-in-oil microemulsions are important for the synthesis of various inorganic materials. In contrast to inverse micelle, water-in-oil micro- emulsion aggregates have mobile or free water in the core of the aggregate (Fig. 2). Reactions take place in a small volume of water inside a microdroplet, which results in improved properties of the products in terms of purity and particle size distribution. Microdroplet size can be controlled by suitable choice and mixing ratio of surfactant and cosurfactant (Fig. 3) and by the chemical composition of the oil and water phases. Microemulsions may have complex phase behaviour, commonly displayed in a phase diagram (Fig. 5 and Fig. 12). Surfactants are amphiphile molecules with hydrophilic head and lypophilic tail, thus bringing them affinity both to water and oil. Their main characteristics are adsorption at the interface and self-organization into supramolecular structures. By forming the interface layer, surfactants decrease surface tension and stabilize the microemulsion. According to the character of the hydrophilic head, surfactants are divided into anionic, cationic, nonionic, and amphoteric. Chemical structures of typical representatives are given in Fig. 6. Microemulsion aggregates may have various shapes, e.g. spherical, ellipsoidal, cylindrical, worm-like or bilayer (Fig. 7). Bicontinuous phase also occurs in different forms, e.g. hexagonal, lamellar or cubic. The main parameters that determines the microstructure are curvature of the interface film. (Fig. 8) and critical packing parameter (Fig. 10). A microemulsion can be composed of microdroplets of oil in water, or microdroplets of water in oil, or it can be the so-called bicontinuous phase in which water and oil are continuously intermixed in a sponge-like structure (Fig. 9). The solubility of water in microemulsion (Fig. 12) as well as morphology of microemulsion aggregates (Fig. 7) are very important for the synthesis of nano particles using microemulsion technique

MicroRNA-146a and AMD3100, two ways to control CXCR4 expression in acute myeloid leukemias

CXCR4 is a negative prognostic marker in acute myeloid leukemias (AMLs). Therefore, it is necessary to develop novel ways to inhibit CXCR4 expression in leukemia. AMD3100 is an inhibitor of CXCR4 currently used to mobilize cancer cells. CXCR4 is a target of microRNA (miR)-146a that may represent a new tool to inhibit CXCR4 expression. We then investigated CXCR4 regulation by miR-146a in primary AMLs and found an inverse correlation between miR-146a and CXCR4 protein expression levels in all AML subtypes. As the lowest miR-146a expression levels were observed in M5 AML, we analyzed the control of CXCR4 expression by miR-146a in normal and leukemic monocytic cells and showed that the regulatory miR-146a/CXCR4 pathway operates during monocytopoiesis, but is deregulated in AMLs. AMD3100 treatment and miR-146a overexpression were used to inhibit CXCR4 in leukemic cells. AMD3100 treatment induces the decrease of CXCR4 protein expression, associated with miR-146a increase, and increases sensitivity of leukemic blast cells to cytotoxic drugs, this effect being further enhanced by miR-146a overexpression. Altogether our data indicate that miR-146a and AMD3100, acting through different mechanism, downmodulate CXCR4 protein levels, impair leukemic cell proliferation and then may be used in combination with anti-leukemia drugs, for development of new therapeutic strategies

The emerging role of MIR-146A in the control of hematopoiesis, immune function and cancer

MicroRNA (miRs) represent a class of small non-coding regulatory RNAs playing a major role in the control of gene expression by repressing protein synthesis at the post-transcriptional level. Studies carried out during the last years have shown that some miRNAs plays a key role in the control of normal and malignant hgematopoiesis. In this review we focus on recent progress in analyzing the functional role of miR-146a in the control of normal and malignant hematopoiesis. On the other hand, this miRNA has shown to impact in the control of innate immune responses. Finally, many recent studies indicate a deregulation of miR-146 in many solid tumors and gene knockout studies indicate a role for this miRNA as a tumor suppressor