WO2008014623A1 - Nanoparticles with a silica-covered metal core - Google Patents

Nanoparticles with a silica-covered metal core Download PDF

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Publication number
WO2008014623A1
WO2008014623A1 PCT/CH2006/000506 CH2006000506W WO2008014623A1 WO 2008014623 A1 WO2008014623 A1 WO 2008014623A1 CH 2006000506 W CH2006000506 W CH 2006000506W WO 2008014623 A1 WO2008014623 A1 WO 2008014623A1
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nanoparticles
silica
metal
alloy
suspension
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PCT/CH2006/000506
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Alke Fink-Petri
Heinrich Hofmann
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Ecole Polytechnique Federale De Lausanne (Epfl)
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Priority to CH00081/09A priority Critical patent/CH697953B1/en
Publication of WO2008014623A1 publication Critical patent/WO2008014623A1/en

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    • C09K11/572—Chalcogenides
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    • G01N33/552—Glass or silica
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    • G01N33/553—Metal or metal coated
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    • G01N33/582—Chemical analysis of biological material, e.g. blood, urine; Testing involving biospecific ligand binding methods; Immunological testing involving labelled substances with fluorescent label
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    • G01N33/585—Chemical analysis of biological material, e.g. blood, urine; Testing involving biospecific ligand binding methods; Immunological testing involving labelled substances with a particulate label, e.g. coloured latex
    • G01N33/587—Nanoparticles
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Definitions

  • the present invention relates to nanoparticles with a metal core, that is to say based on a metal, an alloy or a metal derivative, coated with a silica layer.
  • silica nanoparticles or silica-coated materials by various methods, the best known of which is the so-called Strober method described by W. Stöber, A. Fink and EJ. Bohn in J. Coll. Sci interface. 26 (1968) 62 and by S. H. Im, T. Herricks, YT. Lee, Y. Xia in Chem. Phys. Letters 401 / 1-3 (2005) 19.
  • This synthesis produces monodisperse spherical silica particles using the ethanol solution comprising ammonia, water, and tetraorthosilicate at room temperature.
  • This and other methods have been used to coat various colloidal materials with silica, and have been the subject of many studies over the last decade.
  • amorphous silica has several disadvantages, in particular poorly encapsulate or imprison the metal or metal derivative which is inside, which can lead to incompatibility effects or toxicity vis-à-vis the biological material.
  • the long term one can indeed observe migrations of the material constituting the core outwards through the silica.
  • migration phenomena can occur in the other direction, from the outside to the inside, altering in the long term the properties of the material constituting the core, which is incompatible with certain intended uses.
  • the nanoparticles are sensitive to heat and not stable over time.
  • nanoparticles based on a metal or an alloy or a metal derivative coated with a silica layer, in which the silica is crystalline silica are proposed.
  • crystalline silica mention may be made of quartz, cristobalite or tridymite, these last two crystalline forms being preferred.
  • the terms "coated with”, coated with "or encapsulated in” will be used as synonyms. In the same way, one will speak indifferently of "core” or “heart” for the material which is coated with crystalline silica.
  • a metal an alloy or metal derivative, noble metals, common metals, their oxides, carbides, nitrides, sulphates or selenides.
  • the preparation of the nanoparticles comprises the steps of dispersing metal or alloy nanoparticles of a metal derivative in an alcohol, adding a base to the suspension thus obtained while stirring and then adding an alkoxysilane to the dispersion while maintaining stirring and finally adding water to let the transformation reaction of the alkoxysilane to silica unfold.
  • the nanoparticles thus obtained are coated with an amorphous silica layer.
  • nanoparticles refers to particles having an average diameter generally less than 100-200 nanometers, and nanoparticles having an average particle diameter of between 5 and
  • nanometers preferably between 10 to 15 nanometers for mononuclear nanoparticles.
  • the thickness of the crystallized silica coating layer is not critical to the extent that it is sufficient. It seems that a value of 3 ⁇ m is a minimum and 50 nm is a practical maximum that will obviously reach only for "large" diameters, of the order of 100-200 nanometers.
  • the transformation of the amorphous silica into crystalline silica of the nanoparticles is carried out by a heat treatment at a temperature of between 800 ° C. (preferably greater than 900 ° C.) and 400 ° C., in particular between 100 ° C. and 1 ° C. 250 ° C., the treatment times then being advantageously between 30 minutes and 24 hours.
  • This treatment can be carried out in air or in an inert atmosphere, under nitrogen or argon, for example.
  • the manufacture of nanoparticles is ecological and environmentally friendly. It does not use other solvents than alcohols.
  • nanoparticles using, as alkoxysiloxane, a tetra substituted derivative, a tetraalkylsiloxane or tetraalkoxysilane, the groups of which are advantageously methoxy, ethoxy, propoxy, isopropoxy or isobutoxy groups.
  • nanoparticles whose core metal is gold, silver or alloys of gold or silver which can be used as a pigment, in particular as a pigment for ceramics .
  • the final nanoparticles will obviously have these magnetic properties and can then be used in the separation of biological molecules, in the separation of cells, in the administration of drugs. as well as in the treatment of patients with hyperthermia.
  • the core of the nanoparticles is a metal derivative such as cadmium selenide or zinc sulphide
  • the nanoparticles can be used as non-toxic or fluorescent biomarkers.
  • This example concerns nanoparticles with a gold nucleus.
  • the flask is then placed in an oil bath whose temperature is set at 50 ° C., and the mixture is then stirred with a magnetic stirrer. tetraethylorthosilicate (TEOS) to the mixture.
  • TEOS tetraethylorthosilicate
  • the suspension react at this temperature with stirring for one hour.
  • the flask is removed from the oil bath, the suspension is allowed to cool to room temperature and the magnetic stirrer is removed.
  • the powder is isolated from the suspension by removal of the dispersant under vacuum.
  • Amorphous silica nanoparticles with a gold nucleus are thus obtained, which are heated in air up to 200 ° C. for several hours, until a significant change in the temperature is detected. saturation of the color.
  • nanoparticles can be used as pigments, especially as pigments for ceramics.
  • the ethanol and the tetraorthosilicate can be replaced by another alcohol and another tetraalkylorthosilicate, preferably using the same alkyl radical, for example using tetramethylorthosilicate (TMOS) if methanol is used as alcohol or tetraethylisopropylorthosilicate if used. isopronanol, etc.
  • TMOS tetramethylorthosilicate
  • This example relates to nanoparticles with an iron oxide core.
  • First superparamagnetic iron oxide nanoparticles coated with polyvinyl alcohol are prepared by alkaline coprecipitation of ferric and ferrous chlorides in aqueous solution.
  • solutions of FeCl 3 , 6H 2 O (0.086 M) and FeCl 2 , 4H 2 O (0.043 M) are mixed and precipitated by concentrated ammonia with vigorous stirring.
  • the black precipitate immediately formed is washed several times with ultrapure water until the pH decreases from 10 to 7.
  • the solid is combined and refluxed in a mixture of 0.8 M nitric acid. and aqueous Fe (NO 3 ) 3,9H 2 O 0.21 M for 1 hour.
  • the suspension turns brown and the formation of nitric oxide is observed.
  • the system is then allowed to cool to room temperature, the remaining liquid is removed and 100 ml of ultrapure water is immediately added to the suspension. dispersing immediately.
  • the brown suspension is finally dialyzed for 2 days against a 0.01 M solution of nitric acid, and then stored at 40.degree .
  • iron oxide nanoparticles coated with silica are then prepared under the following conditions: ferrofluid: 3.3 ml of iron oxide nanoparticles as prepared above (dispersion 10 mg iron / ml): ethanol: 10 ml; tetraorthosilicate (TEOS): 250 ⁇ l; (NH 4 OH: 1.5 ml) vessel: 50 ml 3-neck flask under reflux, time: 1 hour, temperature: 50 ° C. in a thermostatic bath, agitation: continuously using a magnetic stirrer rotating at about 300 rpm
  • the ethanol and ammonia are added to the ferrofluid with stirring, then the container is rapidly installed in the thermostatic bath. As soon as possible when the temperature of 50 ° C. is reached, the TEOS is added. After 1 hour of reaction, 25 ml of ultrapure water are added and the container is allowed to cool to room temperature.
  • the size of the particles obtained by applying ultrasound is then reduced. Normally a treatment of 15 minutes is sufficient to ensure a reduction to dimensions of about 200 nm.
  • nanoparticles the silica of which is amorphous, are converted into nanoparticles coated with cristobalite by heating it in air at 100 ° C. for several hours following the crystallization process by X-ray diffraction.
  • nanoparticles thus obtained can be used where strong magnetizations are required, for example in cell separation, DNA purification, organelle extraction, as well as in the treatment of cancer cells by hyperthermia, such as this. is described for example in the disclosure
  • L-cysteine-coated ZnS Mn 2+ fluorescent nanoparticles are prepared by precipitating the sulfide from an aqueous solution in the presence of a surfactant. To do this, a solution of ZnSO4,7H2O (1M, in 0.01MHCl), L-cysteine (0.25M) and MnCl2.4H2O (0.01M, 0.1-0.35% mol) is mixed, that is precipitated with the aid of a solution of Na2S xH2O (pH 13.5) (1 M 1 S2- / Zn2 + 2/10) under a nitrogen atmosphere without stirring.
  • a precipitate of Zn (OH) 2 is first formed under the alkaline shock of the injection of Na2S.
  • the white precipitate thus formed redississed slowly under the formation of ZnS: Mn2 + nanoparticles during the incubation under nitrogen for 30 minutes and by heat treatment at 60 ° C. for 1 hour.
  • the dispersion obtained is transparent and is purified by dialysis against either NaOH (0.01M) or ultrapure water, and the powder is isolated by lyophilization.
  • the nanoparticles are purified by dialyzing for 5 days, under nitrogen, against a solution of 0.01 M NaOH.
  • nanoparticles coated with cristobalite which can be used as any type of biological or biochemical markers (non-toxic fluophores), mainly for proteins, cells, etc.
  • This example relates to multifunctional nanoparticles containing iron oxide cores and manganese-doped zinc sulfide rings.
  • cysteine-coated ZnS: Mn 2 + nanoparticles such as those which are mentioned in the preceding example, immediately after the addition of N (CH 3) 4 OH under stirring by sonication.
  • reaction mixture is removed from the sonication device and the reaction is expected to be complete and the particles cured.
  • the nanoparticles are finished by washing, the amorphous silica of which is converted into cristobalite as indicated in Example 2.
  • the nanoparticles thus obtained can be used when magnetic materials have to be detected optically, in this case by the fluorescence of ZnS: Mn, for example for drug delivery, drug targeting, magnetically assisted transfection, etc.

Abstract

The invention relates to nanoparticles based on a metal, on a metal alloy or on a metal derivative coated with a silica layer, in which the silica is crystalline silica, in particular crystalline silica in the cristobalite form. They may be prepared from nanoparticles based on amorphous silica by making the latter crystallize by a heat treatment in air or in an inert atmosphere at a temperature between 900 and 1400°C and they may be used as pigments for ceramics or in the biological field.

Description

NANOPARTICULES A NOYAU METALLIQUE RECOUVERT DE SILICE NANOPARTICLES WITH METAL CORE COVERED WITH SILICA
La présente invention se rapporte à des nanoparticules à noyau métallique, c'est à dire à base d'un métal, d'un alliage ou d'un dérivé métallique, revêtu d'une couche de silice.The present invention relates to nanoparticles with a metal core, that is to say based on a metal, an alloy or a metal derivative, coated with a silica layer.
On sait fabriquer des nanoparticules de silice ou des matériaux revêtus de silice par diverses méthodes, dont la plus connue est la méthode dite de Strôber décrite par W. Stôber, A. Fink et EJ. Bohn dans J. Coll. Interface Sci. 26 (1968) 62 et par S.H. Im, T. Herricks, YT. Lee, Y. Xia dans Chem. Phys. Letters 401/1-3 (2005) 19. Cette synthèse produit des particules de silice sphériques monodispersées en utilisant la solution d'éthanol comprenant, de l'ammoniaque, de l'eau, et du tétraorthosilicate à température ambiante. Cette méthode, ainsi que d'autres, ont été utilisées pour revêtir divers matériaux colloïdaux par de la silice, et ont fait l'objet de nombreuses études durant ces dix dernières années. On citera aussi la voie de synthèse indirecte décrite par Homori et Matijevic dans J. Colloid Interface Sci. 160, 288 (1993) pour préparer des nanoparticules de fer enrobées de silice qui utilisent la réduction du noyau dans un four en présence d'hydrogène.It is known to manufacture silica nanoparticles or silica-coated materials by various methods, the best known of which is the so-called Strober method described by W. Stöber, A. Fink and EJ. Bohn in J. Coll. Sci interface. 26 (1968) 62 and by S. H. Im, T. Herricks, YT. Lee, Y. Xia in Chem. Phys. Letters 401 / 1-3 (2005) 19. This synthesis produces monodisperse spherical silica particles using the ethanol solution comprising ammonia, water, and tetraorthosilicate at room temperature. This and other methods have been used to coat various colloidal materials with silica, and have been the subject of many studies over the last decade. There is also the indirect synthesis route described by Homori and Matijevic in J. Colloid Interface Sci. 160, 288 (1993) to prepare silica coated iron nanoparticles which utilize ring reduction in an oven in the presence of hydrogen.
Toutes ces méthodes ont jusqu'à présent abouti à des nanoparticules à noyau métallique revêtu de silice amorphe.All of these methods have so far resulted in metal core nanoparticles coated with amorphous silica.
Or, la silice amorphe présente plusieurs désavantages, en particulier de mal encapsuler ou emprisonner le métal ou le dérivé métallique qui se trouve à l'intérieur, ce qui peut conduire à des effets d'incompatibilité ou de toxicité vis-à-vis de la matière biologique. A long terme, on peut en effet observer des migrations du matériau constituant le noyau vers l'extérieur à travers la silice. De même, des phénomènes de migration peuvent intervenir dans l'autre sens, de l'extérieur vers l'intérieur, altérant à la longue les propriétés du matériau constituant le noyau, ce qui est incompatible avec certains usages envisagés. De plus, en règle générale, les nanoparticules sont sensibles à la chaleur et peu stables dans le temps.However, amorphous silica has several disadvantages, in particular poorly encapsulate or imprison the metal or metal derivative which is inside, which can lead to incompatibility effects or toxicity vis-à-vis the biological material. In the long term, one can indeed observe migrations of the material constituting the core outwards through the silica. Similarly, migration phenomena can occur in the other direction, from the outside to the inside, altering in the long term the properties of the material constituting the core, which is incompatible with certain intended uses. In addition, as a rule, the nanoparticles are sensitive to heat and not stable over time.
Selon l'invention au contraire, on propose des nanoparticules à base d'un métal ou d'un alliage ou d'un dérivé métallique revêtu d'une couche de silice, dans laquelle la silice est de la silice cristalline. Comme exemple de silice cristalline, on peut citer le quartz, la cristobalite ou la tridymite, ces deux dernières formes cristallines étant préférées. Aux fins de l'invention, précisons ici que seront utilisés comme synonymes les termes "revêtu de", enrobé de" ou encapsulé dans". De même, on parlera indifféremment de "noyau" ou de "coeur" pour le matériau qui est enrobé de silice cristalline.According to the invention, on the contrary, nanoparticles based on a metal or an alloy or a metal derivative coated with a silica layer, in which the silica is crystalline silica, are proposed. As an example of crystalline silica, mention may be made of quartz, cristobalite or tridymite, these last two crystalline forms being preferred. For the purpose of the invention, it should be noted here that the terms "coated with", coated with "or encapsulated in" will be used as synonyms. In the same way, one will speak indifferently of "core" or "heart" for the material which is coated with crystalline silica.
Selon les applications envisagées, on pourra utiliser comme noyau un métal, un alliage ou dérivé métallique, des métaux nobles, des métaux communs, leurs oxydes, carbures, nitrures, sulfates ou séléniures.Depending on the applications envisaged, it will be possible to use as the core a metal, an alloy or metal derivative, noble metals, common metals, their oxides, carbides, nitrides, sulphates or selenides.
La préparation des nanoparticules, objet également de l'invention, comprend des étapes consistant à disperser des nanoparticules en métal ou en alliage d'un dérivé métallique dans un alcool, à ajouter une base à la suspension ainsi obtenue tout en agitant, puis à ajouter un alcoxysilane à la dispersion tout en maintenant l'agitation et enfin à ajouter de l'eau pour laisser la réaction de transformation de l'alcoxysilane en silice se dérouler.The preparation of the nanoparticles, which is also the subject of the invention, comprises the steps of dispersing metal or alloy nanoparticles of a metal derivative in an alcohol, adding a base to the suspension thus obtained while stirring and then adding an alkoxysilane to the dispersion while maintaining stirring and finally adding water to let the transformation reaction of the alkoxysilane to silica unfold.
Une fois isolées, les nanoparticules ainsi obtenues sont enrobées d'une couche de silice amorphe.Once isolated, the nanoparticles thus obtained are coated with an amorphous silica layer.
Comme on le sait, on désigne par nanoparticules, des particules ayant un diamètre moyen généralement inférieur à 100-200 nanomètres et on s'intéressera de préférence aux nanoparticules ayant un diamètre moyen de particules compris entre 5 etAs is known, the term "nanoparticles" refers to particles having an average diameter generally less than 100-200 nanometers, and nanoparticles having an average particle diameter of between 5 and
25 nanomètres, de préférence entre 10 à 15 nanomètres pour des nanoparticules mononucléaires.25 nanometers, preferably between 10 to 15 nanometers for mononuclear nanoparticles.
L'épaisseur de la couche de silice cristallisée d'enrobage n'est pas critique dans la mesure où celle-ci est suffisante. Il semble qu'une valeur de 3 πm soit un minimum et 50 nm soit un maximum pratique qu'on n'atteindra évidemment que pour des "grands" diamètres, de l'ordre de 100-200 nanomètres.The thickness of the crystallized silica coating layer is not critical to the extent that it is sufficient. It seems that a value of 3 πm is a minimum and 50 nm is a practical maximum that will obviously reach only for "large" diameters, of the order of 100-200 nanometers.
La transformation de la silice amorphe en silice cristallisée des nanoparticules est réalisée par un traitement thermique à une température comprise entre 8000C (de préférence supérieure à 900°C) et l'4000C, notamment entre l'1000C et l'2500C, les temps de traitement étant alors avantageusement compris entre 30 minutes et 24 heures.The transformation of the amorphous silica into crystalline silica of the nanoparticles is carried out by a heat treatment at a temperature of between 800 ° C. (preferably greater than 900 ° C.) and 400 ° C., in particular between 100 ° C. and 1 ° C. 250 ° C., the treatment times then being advantageously between 30 minutes and 24 hours.
Ce traitement peut se réaliser à l'air ou en atmosphère inerte, sous azote ou argon par exemple. Au nombre des avantages du procédé selon l'invention, on retiendra immédiatement que la fabrication des nanoparticules est écologique et respectueuse de l'environnement. Elle n'utilise en effet pas d'autres solvants que des alcools.This treatment can be carried out in air or in an inert atmosphere, under nitrogen or argon, for example. Among the advantages of the process according to the invention, it should be noted immediately that the manufacture of nanoparticles is ecological and environmentally friendly. It does not use other solvents than alcohols.
On peut ainsi préparer des nanoparticules en utilisant comme alcoxysiloxane un dérivé tétra substitué, un tétraalkylsiloxane ou tétraalcoyxsilane dont les groupes sont avantageusement des groupes méthoxy, éthoxy, propoxy, isopropoxy ou isobutoxy.It is thus possible to prepare nanoparticles using, as alkoxysiloxane, a tetra substituted derivative, a tetraalkylsiloxane or tetraalkoxysilane, the groups of which are advantageously methoxy, ethoxy, propoxy, isopropoxy or isobutoxy groups.
Par ce procédé, il est possible de préparer des nanoparticules dont le métal constituant le noyau est de l'or, de l'argent ou des alliages d'or ou d'argent qui peuvent être utilisées comme pigment, en particulier comme pigment pour céramiques.By this process, it is possible to prepare nanoparticles whose core metal is gold, silver or alloys of gold or silver which can be used as a pigment, in particular as a pigment for ceramics .
En utilisant au cœur l'oxyde de fer ou un oxyde d'un métal magnétique, les nanoparticules finales présenteront évidemment ces propriétés magnétiques et pourront alors être utilisées dans la séparation de molécules biologiques, dans la séparation de cellules, dans l'administration de médicaments ainsi que dans le traitement de patients par hyperthermie.By using iron oxide or an oxide of a magnetic metal at the core, the final nanoparticles will obviously have these magnetic properties and can then be used in the separation of biological molecules, in the separation of cells, in the administration of drugs. as well as in the treatment of patients with hyperthermia.
Si le cœur des nanoparticules est un dérivé métallique tel que du séléniure de cadmium ou du sulfure de zinc, les nanoparticules pourront être utilisées comme biomarqueurs non toxiques ou fluophores.If the core of the nanoparticles is a metal derivative such as cadmium selenide or zinc sulphide, the nanoparticles can be used as non-toxic or fluorescent biomarkers.
Enfin, il est également possible d'associer les particules, soit avant leur fabrication, soit après leur fabrication par simple mélange, par exemple entre des nanoparticules à oxydes de fer et celles en séléniures de cadmium au sulfure de zinc pour obtenir des particules multifonctionnelles dans des applications biologiques.Finally, it is also possible to associate the particles, either before their manufacture or after their manufacture by simple mixing, for example between nanoparticles with iron oxides and those with zinc sulphide cadmium selenides to obtain multifunctional particles in biological applications.
L'invention sera mieux comprise en référence aux exemples qui suivent, donnés à titre d'exemples non limitatifs.The invention will be better understood with reference to the examples which follow, given by way of non-limiting examples.
Exemple 1Example 1
Cet exemple concerne des nanoparticules à noyau d'or. On place dans un ballon 10 ml d'une suspension d'or (BB International, colloïde d'or, 15 nanomètres C=5.5 10"5 G or/ml) et on ajoute en agitant 400 ml d'éthanol (Merck, absolu pour analyse) et 30 ml d'ammoniaque à 28 %. On place alors le ballon dans un bain d'huile dont la température est réglée à 50° C, puis on agite le mélange avec un agitateur magnétique. On ajoute alors rapidement 5 ml de tétraéthylorthosilicate (TEOS) au mélange. On laisse la suspension réagir à cette température sous agitation pendant une heure. Après quoi, on sort le ballon du bain d'huile, on laisse refroidir la suspension à la température ambiante et on retire l'agitateur magnétique. On isole la poudre de la suspension par élimination du dispersant sous vide.This example concerns nanoparticles with a gold nucleus. 10 ml of a gold suspension (BB International, gold colloid, 15 nanometers C = 5.5 × 10 -5 G gold / ml) are placed in a flask and 400 ml of ethanol are added with stirring (Merck, absolute for analysis) and 30 ml of 28% ammonia The flask is then placed in an oil bath whose temperature is set at 50 ° C., and the mixture is then stirred with a magnetic stirrer. tetraethylorthosilicate (TEOS) to the mixture. the suspension react at this temperature with stirring for one hour. After that, the flask is removed from the oil bath, the suspension is allowed to cool to room temperature and the magnetic stirrer is removed. The powder is isolated from the suspension by removal of the dispersant under vacuum.
On obtient ainsi des nanoparticules de silice amorphe à noyau d'or, que l'on fait chauffer à l'air jusqu'à l'2000C pendant plusieurs heures, jusqu'à ce que l'on détecte un changement important dans la saturation de la couleur.Amorphous silica nanoparticles with a gold nucleus are thus obtained, which are heated in air up to 200 ° C. for several hours, until a significant change in the temperature is detected. saturation of the color.
Une analyse par diffraction des rayons X montre alors que la silice amorphe de la couche enrobant l'or a été modifiée en cristobalite par le chauffage.An X-ray diffraction analysis then shows that the amorphous silica of the gold-coating layer has been changed to cristobalite by heating.
Ces nanoparticules peuvent être utilisées comme pigments, notamment comme pigments pour des céramiques.These nanoparticles can be used as pigments, especially as pigments for ceramics.
On peut remplacer l'éthanol et le tétraorthosilicate, par un autre alcool et un autre tétraalkylorthosilicate, de préférence en utilisant le même reste alkyle, par exemple en utilisant le tétraméthylorthosilicate (TMOS) si on utilise du méthanol comme alcool ou du tétraéthylisopropylorthosilicate si on utilise de l'isopronanol, etc.The ethanol and the tetraorthosilicate can be replaced by another alcohol and another tetraalkylorthosilicate, preferably using the same alkyl radical, for example using tetramethylorthosilicate (TMOS) if methanol is used as alcohol or tetraethylisopropylorthosilicate if used. isopronanol, etc.
On peut aussi remplacer l'ammoniaque par une solution aqueuse de soude ou de potasse.It is also possible to replace the ammonia with an aqueous solution of soda or potash.
Exemple 2Example 2
Cet exemple concerne des nanoparticules à noyau d'oxyde de fer. On prépare d'abord des nanoparticules d'oxyde de fer superparamagnétique revêtues d'alcool polyvinylique par coprécipitation alcaline de chlorures ferrique et ferreux en solution aqueuse. Pour ce faire, on mélange des solutions de FeCI3,6H2O (0,086 M) et FeCI2,4H2O (0,043 M) qu'on fait précipiter par de l'ammoniaque concentrée en agitant vigoureusement. On lave plusieurs fois à l'eau ultra-pure le précipité noir immédiatement formé jusqu'à ce que le pH diminue de 10 à 7. On réunit le solide et on le porte à reflux dans un mélange d'acide nitrique 0,8 M et de Fe(NO3)3,9H2O 0,21 M aqueux pendant 1 heure. Durant cette étape la suspension vire au brun et on observe la formation d'oxyde nitrique. On laisse alors refroidir le système à température ambiante, on élimine le liquide restant et on ajoute immédiatement à la suspension 100 ml d'eau ultra-pure en la dispersant immédiatement. On dialyse enfin la suspension brune pendant 2 jours contre une solution 0,01 M d'acide nitrique, puis on stocke à 40C.This example relates to nanoparticles with an iron oxide core. First superparamagnetic iron oxide nanoparticles coated with polyvinyl alcohol are prepared by alkaline coprecipitation of ferric and ferrous chlorides in aqueous solution. To do this, solutions of FeCl 3 , 6H 2 O (0.086 M) and FeCl 2 , 4H 2 O (0.043 M) are mixed and precipitated by concentrated ammonia with vigorous stirring. The black precipitate immediately formed is washed several times with ultrapure water until the pH decreases from 10 to 7. The solid is combined and refluxed in a mixture of 0.8 M nitric acid. and aqueous Fe (NO 3 ) 3,9H 2 O 0.21 M for 1 hour. During this stage the suspension turns brown and the formation of nitric oxide is observed. The system is then allowed to cool to room temperature, the remaining liquid is removed and 100 ml of ultrapure water is immediately added to the suspension. dispersing immediately. The brown suspension is finally dialyzed for 2 days against a 0.01 M solution of nitric acid, and then stored at 40.degree .
On prépare alors les nanoparticules d'oxyde de fer revêtues de silice dans les conditions suivantes : ferrofluide: 3,3 ml de nanoparticules d'oxyde de fer comme préparées ci-dessus (dispersion 10 mg fer/ml) : éthanol: 10 ml ; tétraorthosilicate (TEOS): 250 μl ; (NH4OH: 1 ,5 ml ; récipient: 50 ml ballon à 3 cols sous reflux ; durée : 1 heure ; température: 50 0C en bain thermostatique ; agitation: en continu en utilisant un agitateur magnétique tournant à environ 300 tr/mnThe iron oxide nanoparticles coated with silica are then prepared under the following conditions: ferrofluid: 3.3 ml of iron oxide nanoparticles as prepared above (dispersion 10 mg iron / ml): ethanol: 10 ml; tetraorthosilicate (TEOS): 250 μl; (NH 4 OH: 1.5 ml) vessel: 50 ml 3-neck flask under reflux, time: 1 hour, temperature: 50 ° C. in a thermostatic bath, agitation: continuously using a magnetic stirrer rotating at about 300 rpm
On ajoute l'éthanol et l'ammoniaque au ferrofluide sous agitation, puis on installe rapidement le récipient dans le bain thermostatique. Dès que possible quand la température de 5O0C est atteinte, on ajoute le TEOS. Après 1 heure de réaction, on ajoute 25 ml d'eau ultra-pure et on laisse refroidir le récipient à température ambiante.The ethanol and ammonia are added to the ferrofluid with stirring, then the container is rapidly installed in the thermostatic bath. As soon as possible when the temperature of 50 ° C. is reached, the TEOS is added. After 1 hour of reaction, 25 ml of ultrapure water are added and the container is allowed to cool to room temperature.
On procède alors à une réduction de la taille des particules obtenues par application d'ultrasons. Normalement un traitement de 15 minutes est suffisant pour assurer une réduction à des dimensions d'environ 200 nm.The size of the particles obtained by applying ultrasound is then reduced. Normally a treatment of 15 minutes is sufficient to ensure a reduction to dimensions of about 200 nm.
On transforme ces nanoparticules dont la silice est amorphe en nanoparticules enrobées de cristobalite en chauffant celle-ci à l'air à l'1000C pendant plusieurs heures en suivant le processus de cristallisation par diffraction aux rayons X.These nanoparticles, the silica of which is amorphous, are converted into nanoparticles coated with cristobalite by heating it in air at 100 ° C. for several hours following the crystallization process by X-ray diffraction.
Les nanoparticules ainsi obtenues peuvent être utilisées là où de fortes magnétisations sont requises, par exemple dans la séparation de cellules, la purification d'ADN, l'extraction d'organelles, ainsi que dans le traitement de cellules cancéreuses par hyperthermie, tel que cela est décrit par exemple dans l'exposé d'inventionThe nanoparticles thus obtained can be used where strong magnetizations are required, for example in cell separation, DNA purification, organelle extraction, as well as in the treatment of cancer cells by hyperthermia, such as this. is described for example in the disclosure
PCT/EP2005/005553.PCT / EP2005 / 005553.
Exemple 3Example 3
Cet exemple se rapporte à des nanoparticules à noyau de sulfure dopé au manganèse On prépare des nanoparticules fluorescentes de ZnS:Mn2+ revêues de L- cystéine en précipitant le sulfure d'une solution aqueuse en présence d'un surfactant. Pour ce faire, on mélange une solution de ZnSO4,7H2O (1M, in 0,01 M HCI), L-cystéine (0,25M) et MnCI2,4H2O (0,01 M, 0,1-0.35 %mol), que l'on fait précipiter à l'aide d'une solution de Na2S xH2O (pH 13,5) (1 M1 S2-/Zn2+ 2/10) sous atmosphère d'azote sans agiter. Un précipité de Zn(OH)2 se forme d'abord sous le choc alcalin de l'injection de Na2S. Le précipité blanc ainsi formé se redissout lentement sous la formation de nanoparticules de ZnS:Mn2+ durant l'incubation sous azote pendant 30 minutes et par traitement thermique à 60°C pendant 1 heure. La dispersion obtenue est transparente et on la purifie par dialyse contre soit NaOH (0,01M) soit de l'eau ultra-pure, et la poudre est isolée par lyophilisation.This example relates to manganese doped sulfide core nanoparticles. L-cysteine-coated ZnS: Mn 2+ fluorescent nanoparticles are prepared by precipitating the sulfide from an aqueous solution in the presence of a surfactant. To do this, a solution of ZnSO4,7H2O (1M, in 0.01MHCl), L-cysteine (0.25M) and MnCl2.4H2O (0.01M, 0.1-0.35% mol) is mixed, that is precipitated with the aid of a solution of Na2S xH2O (pH 13.5) (1 M 1 S2- / Zn2 + 2/10) under a nitrogen atmosphere without stirring. A precipitate of Zn (OH) 2 is first formed under the alkaline shock of the injection of Na2S. The white precipitate thus formed redississed slowly under the formation of ZnS: Mn2 + nanoparticles during the incubation under nitrogen for 30 minutes and by heat treatment at 60 ° C. for 1 hour. The dispersion obtained is transparent and is purified by dialysis against either NaOH (0.01M) or ultrapure water, and the powder is isolated by lyophilization.
Pour revêtir les particules de la poudre avec de la silice, on ajoute à une dispersion de celles-ci du 3-(mercaptopropyl)méthoxysilane (1 mM), en agitant pendantTo coat the particles of the powder with silica, 3- (mercaptopropyl) methoxysilane (1 mM) is added to a dispersion thereof, stirring for
1 nuit pour remplacer partiellement la cystéine, puis on ajoute du silicate de sodium1 night to partially replace the cysteine, then add sodium silicate
(SiO2- NaOH) et, finalement, on purifie les nanoparticules en dialysant pendant 5 jours, sous azote, contre une solution de NaOH.0,01 M.(SiO2-NaOH) and, finally, the nanoparticles are purified by dialyzing for 5 days, under nitrogen, against a solution of 0.01 M NaOH.
La silice amorphe enrobant les nanoparticules ainsi obtenue est cristallisée comme décrit dans l'exemple 2. On obtient ainsi des nanoparticules enrobées de cristobalite, qui peuvent être utilisées comme tout type de marqueurs biologiques ou biochimiques (fluophores non toxiques), principalement pour des protéines, des cellules, etc.The amorphous silica coating the nanoparticles thus obtained is crystallized as described in Example 2. This gives nanoparticles coated with cristobalite, which can be used as any type of biological or biochemical markers (non-toxic fluophores), mainly for proteins, cells, etc.
Exemple 4Example 4
Cet exemple se rapporte à des nanoparticules multifonctionnelles contenant des noyaux d'oxyde de fer et des noyaux de sulfure de zinc dopés au manganèse.This example relates to multifunctional nanoparticles containing iron oxide cores and manganese-doped zinc sulfide rings.
On mélange 15 μl d'une dispersion de nanoparticules d'oxyde de fer à une concentration allant de 1 à 25 mg/ml en fer revêtu soit avec de l'acide citrique soit de l'alcool polyvinylique (PVA) avec une solution 0,002 M de sodium-bis(2- éthylhéxyl)sulfosuccinate (AOT, Fluka) contenant de l'octane, puis on émulsionne les particules revêtues en phase continue pendant 30 minutes par traitement aux ultrasons (Telsonic, DG-100, 100 W, 36 Hz). On ajoute alors 15 μl de TMOS préhydrolysé pendant 10 minutes et d'un rapport moléculaire de TMOS:MeOH:H20 of 1 :22:6 d'une concentration nette de 2 x 10"3 M HCI. On continue le traitement aux ultrasons de la dispersion pendant 5 minutes, après quoi on ajoute 3 μl d'hydroxide de tétraméthylammonium (N(CH3)4OH, 0.25% w/w; Fluka) toujours sous traitement aux ultrasons pour l'initiation de la réaction de condensation.15 .mu.l of a dispersion of iron oxide nanoparticles at a concentration ranging from 1 to 25 mg / ml of iron coated with either citric acid or polyvinyl alcohol (PVA) with a 0.002M solution are mixed. octane-containing sodium-bis (2-ethylhexyl) sulfosuccinate (AOT, Fluka) and then the coated particles are emulsified in continuous phase for 30 minutes by sonication (Telsonic, DG-100, 100 W, 36 Hz) . 15 μl of prehydrolysed TMOS are then added for 10 minutes and a molecular ratio of TMOS: MeOH: H 2 O of 1: 22: 6 at a net concentration of 2 × 10 -3 MHCl. the dispersion for 5 minutes, after which 3 μl of tetramethylammonium hydroxide (N (CH 3 ) 4 OH, 0.25% w / w, Fluka) is always added under sonication treatment for the initiation of the condensation reaction.
Si on désire préparer des nanoparticules multifonctionnelles, on ajoute alors des nanoparticules de ZnS:Mn2+ enrobées de cystéine, telles que celles qui sont mentionnées à l'exemple précédent, immédiatement après l'addition du N(CH3)4OH sous agitation par traitement aux ultrasons.If it is desired to prepare multifunctional nanoparticles, cysteine-coated ZnS: Mn 2 + nanoparticles, such as those which are mentioned in the preceding example, immediately after the addition of N (CH 3) 4 OH under stirring by sonication.
Après 25 minutes, on sort le mélange réactionnel du dispositif de traitement aux ultrasons et la réaction est censée être complète et les particules durcies. On laisse reposer 30 minutes et on purifie les particules en les lavant avec 3 ml d'eau sur un aimant permanent statique (Maurer Magnets, Switzerland, Br = 350 mT) de néodyme- fer-bore (NdFeB).After 25 minutes, the reaction mixture is removed from the sonication device and the reaction is expected to be complete and the particles cured. The mixture is left standing for 30 minutes and the particles are purified by washing with 3 ml of water on a static permanent magnet (Maurer Magnets, Switzerland, Br = 350 mT) of neodymium iron boron (NdFeB).
Après 30 minutes encore, on termine en lavant les nanoparticules, dont on transforme la silice amorphe en cristobalite comme indiqué dans l'exemple 2.After another 30 minutes, the nanoparticles are finished by washing, the amorphous silica of which is converted into cristobalite as indicated in Example 2.
Les nanoparticules ainsi obtenues peuvent être utilisées quand des matériaux magnétiques doivent être détectés optiquement, soit dans ce cas précis par la fluorescence de ZnS:Mn, par exemple pour la délivrance de médicaments, le ciblage de médicaments, la transfection assistée magnétiquement, etc. The nanoparticles thus obtained can be used when magnetic materials have to be detected optically, in this case by the fluorescence of ZnS: Mn, for example for drug delivery, drug targeting, magnetically assisted transfection, etc.

Claims

REVENDICATIONS
1. Nanoparticules à base d'un métal, d'un alliage ou d'un dérivé métallique revêtu d'une couche de silice, caractérisées en ce que la silice est de la silice cristalline.1. Nanoparticles based on a metal, an alloy or a metal derivative coated with a silica layer, characterized in that the silica is crystalline silica.
2. Nanoparticules selon la revendication 1 , caractérisées en ce que la silice cristalline est sous la forme cristobalite ou tridymite.2. Nanoparticles according to claim 1, characterized in that the crystalline silica is in the form cristobalite or tridymite.
3. Nanoparticules selon la revendication 1 ou 2, caractérisées en ce que le métal, l'alliage ou le dérivé métallique est choisi dans le groupe comprenant les métaux nobles, les métaux communs, leurs oxydes, carbures, nitrures, sulfures et séléniures.3. Nanoparticles according to claim 1 or 2, characterized in that the metal, alloy or metal derivative is selected from the group consisting of noble metals, base metals, their oxides, carbides, nitrides, sulfides and selenides.
4. Nanoparticules selon la revendication 3, caractérisées en ce que le métal, l'alliage ou le dérivé métallique est de l'oxyde de fer, du séléniure de cadmium, du sulfure de zinc ou leurs mélanges.4. Nanoparticles according to claim 3, characterized in that the metal, the alloy or the metal derivative is iron oxide, cadmium selenide, zinc sulphide or mixtures thereof.
5 Procédé de fabrication de nanoparticules selon la revendication 1 comprenant les étapes consistant àA process for producing nanoparticles according to claim 1 comprising the steps of
- disperser des nanoparticules d'un métal, d'un alliage ou d'un dérivé métallique dans un alcool,dispersing nanoparticles of a metal, an alloy or a metal derivative in an alcohol,
- ajouter à la suspension une base ainsi obtenue tout en agitant,- add to the suspension a base thus obtained while stirring,
- ajouter un alcoxysilane à la suspension sous agitation,add an alkoxysilane to the suspension with stirring,
- puis ajouter de l'eau et laisser la réaction de transformation de Palcoxysilane en silice se dérouler,then add water and let the reaction of transformation of the alkoxysilane into silica proceed,
les nanoparticules obtenues dans la suspension comprenant un ou plusieurs noyaux de métal, d'alliage ou de dérivé métallique enrobés dans de la silice amorphe, etthe nanoparticles obtained in the suspension comprising one or more cores of metal, alloy or metal derivative embedded in amorphous silica, and
- isoler les nanoparticules du mélange réactionnel,isolating the nanoparticles from the reaction mixture,
- puis cristalliser la silice amorphe qui les recouvre par traitement thermique.- Then crystallize the amorphous silica which covers them by heat treatment.
6. Procédé selon la revendication 5, caractérisé en ce que l'alcoxysilane est choisi dans le groupe comprenant les tétraalcoxysilanes, les groupes alcoxy étant méthoxy, éthoxy, propoxy, isopropoxy ou isobutoxy, et les dérivés mercapto de ceux-ci. 6. Process according to claim 5, characterized in that the alkoxysilane is chosen from the group comprising tetraalkoxysilanes, the alkoxy groups being methoxy, ethoxy, propoxy, isopropoxy or isobutoxy, and the mercapto derivatives thereof.
7. Procédé de fabrication selon l'une des revendications précédentes, caractérisé en ce que l'alcool est le méthanol, l'éthanol, le propanol, l'isopropanol ou l'isobutanol.7. Production method according to one of the preceding claims, characterized in that the alcohol is methanol, ethanol, propanol, isopropanol or isobutanol.
8. Procédé de fabrication selon l'une des revendications précédentes, caractérisé en ce que la base est de l'ammoniaque.8. Manufacturing process according to one of the preceding claims, characterized in that the base is ammonia.
9. Procédé de fabrication selon l'une des revendications précédentes, caractérisé en ce que le traitement thermique est réalisé à l'air ou sous atmosphère inerte à une température comprise entre 900 et l'4000C.9. Manufacturing process according to one of the preceding claims, characterized in that the heat treatment is carried out in air or in an inert atmosphere at a temperature between 900 and 400 0 C.
10. Utilisation des nanoparticules selon l'une des revendications 1 à 9 comme pigment de céramiques10. Use of the nanoparticles according to one of claims 1 to 9 as a ceramic pigment
11. Utilisation des nanoparticules selon l'une des revendications 1 à 9 dans les traitements magnétiques de cellules, notamment de cellules cancéreuses, de la séparation de cellules, de l'extraction d'organelles et de la purification d'ADN .11. Use of the nanoparticles according to one of claims 1 to 9 in the magnetic treatments of cells, including cancer cells, cell separation, organelles extraction and DNA purification.
12. Utilisation des nanoparticules selon l'une des revendications 1 à 9 comme marqueurs fluorescents non toxiques. 12. Use of the nanoparticles according to one of claims 1 to 9 as non-toxic fluorescent markers.
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Cited By (3)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
EP2103572A1 (en) 2008-03-19 2009-09-23 Rolex Sa Enamel
WO2011035446A1 (en) 2009-09-22 2011-03-31 Rolex S.A. Composite material dyed by nanoparticles
US9408912B2 (en) 2011-08-10 2016-08-09 Magforce Ag Agglomerating magnetic alkoxysilane-coated nanoparticles

Citations (2)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
WO2003057359A2 (en) * 2002-01-07 2003-07-17 The University Of Reading Microparticles and methods for their production
US20030157330A1 (en) * 2001-09-20 2003-08-21 Ostafin Agnes E. Process for making mesoporous silicate nanoparticle coatings and hollow mesoporous silica nano-shells

Patent Citations (2)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
US20030157330A1 (en) * 2001-09-20 2003-08-21 Ostafin Agnes E. Process for making mesoporous silicate nanoparticle coatings and hollow mesoporous silica nano-shells
WO2003057359A2 (en) * 2002-01-07 2003-07-17 The University Of Reading Microparticles and methods for their production

Non-Patent Citations (6)

* Cited by examiner, † Cited by third party
Title
ALCALA ET AL: "Synthesis based on the wet impregnation method and characterization of iron and iron oxide-silica nanocomposites", SOLID STATE IONICS, NORTH HOLLAND PUB. COMPANY. AMSTERDAM, NL, vol. 177, no. 9-10, 31 March 2006 (2006-03-31), pages 955 - 960, XP005389852, ISSN: 0167-2738 *
F.GARCIA-SANTAMARIA, V.SALGUERINO-MACEIRA, C. LOPEZ, L.M. LIZ-MARZAN: "Synthetic opals based on silica coated gold nanoparticles."", LANGMUIR, vol. 18, 5 February 2002 (2002-02-05), pages 4519 - 4522, XP002429513 *
JOHANNSEN M ET AL: "Thermotherapy using magnetic nanoparticles combined with external radiation in an orthotopic rat model of prostate cancer", PROSTATE, WILEY-LISS, NEW YORK, NY, US, vol. 66, no. 1, 1 January 2006 (2006-01-01), pages 97 - 104, XP008066501, ISSN: 0270-4137 *
LIU ET AL: "Surface-functionalized silica-coated gold nanoparticles and their bioapplications", TALANTA, ELSEVIER, AMSTERDAM, NL, vol. 67, no. 3, 15 September 2005 (2005-09-15), pages 456 - 461, XP005047812, ISSN: 0039-9140 *
PALOMARES SANCHEZ S A ET AL: "Quantitative analysis of iron oxide particles embedded in an amorphous xerogel matrix", JOURNAL OF NON-CRYSTALLINE SOLIDS, NORTH-HOLLAND PHYSICS PUBLISHING. AMSTERDAM, NL, vol. 325, no. 1-3, 15 September 2003 (2003-09-15), pages 251 - 257, XP004448269, ISSN: 0022-3093 *
XU J ET AL: "Iron oxide-silica nanocomposites via sol-gel processing", MATERIALS LETTERS, NORTH HOLLAND PUBLISHING COMPANY. AMSTERDAM, NL, vol. 58, no. 11, April 2004 (2004-04-01), pages 1696 - 1700, XP004495331, ISSN: 0167-577X *

Cited By (6)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
EP2103572A1 (en) 2008-03-19 2009-09-23 Rolex Sa Enamel
US8329779B2 (en) 2008-03-19 2012-12-11 Rolex S.A. Enamel
WO2011035446A1 (en) 2009-09-22 2011-03-31 Rolex S.A. Composite material dyed by nanoparticles
EP2305756A1 (en) 2009-09-22 2011-04-06 Rolex Sa Coloured composite material containing nanoparticles
US9408912B2 (en) 2011-08-10 2016-08-09 Magforce Ag Agglomerating magnetic alkoxysilane-coated nanoparticles
US9962442B2 (en) 2011-08-10 2018-05-08 Magforce Ag Agglomerating magnetic alkoxysilane-coated nanoparticles

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