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European Cells and Materials Vol. 3. Suppl.

2, 2002 (pages 110-113) ISSN 1473-2262

S. Mornet, F. Grasset*, J. Portier and E. Duguet
Institut de Chimie de la Matière Condensée de Bordeaux ICMCB-CNRS, Université Bordeaux-1, 87 avenue du Dr
Albert Schweitzer, F-33608 Pessac, France * Current address: Laboratoire des Verres et Céramiques, Institut de
Chimie de Rennes, Université Rennes-1, Campus de Beaulieu,
F-35042 Rennes, France
INTRODUCTION numerous commercially available alkoxysilane
There is a great deal of interest in investigating new
synthetic routes, controlling the size and the The synthetic method was derived from the Stöber
morphology, and understanding the overall behavior process of silica nanoparticles synthesis (based on
of nanoparticles. Magnetic nanoparticles are being the base-catalyzed polycondensation of
studied in particular for their current and future tetraalkoxysilane) and developed in reverse
applications in biology and medicine, including microemulsion conditions [3]. This technique relies
magnetic cell separation, magnetic resonance on the self-assembly nature of surfactants to push
imaging contrast enhancement, magnetic transport aqueous reactant into micelles. Due to the dynamic
of anti-cancer drugs [1]. nature of micelles, aqueous components (including
In this field and especially for in vivo applications, maghemite nanoparticles) can come together and
the main challenges currently consist in (i) reducing react to form particles, which are constrained to the
the nanoparticle size for going through the majority micelle size.
of biological membranes, (ii) ensuring their stability The goals of the present study are to (i) control the
in pH conditions of biological fluids and (iii) γ-Fe2O3@SiO2 morphology thanks to the synthesis
tailoring their surface in order to functionalize conditions, (ii) investigate their stability in water,
and/or develop strong interactions with specific their thermal behavior and their magnetic properties
biological components (dye, drug or effector and (iii) use them, secondarily, as precursors for
grafting). silica hollow nanospheres, obtained by a
The magnetic nanoparticles, which are the most discriminatory dissolution of the magnetic cores.
frequently studied, belong to the ferrite family,
especially magnetite (Fe3O4) and maghemite (γ-
Fe2O3). Many studies focused on ferrofluids, which METHODS
are colloidal aqueous solutions (sols) of Materials: all the chemicals (from Aldrich) were of
monodomain magnetic particles. Ferrofluids reagent grade and used without further purification.
necessitate a sufficient electrostatic repulsion
between particles [2]. Nevertheless, the zero point Ferrofluid synthesis: cationic γ-Fe2O3 aqueous sols
of charge (ZPC) of these iron oxides is close to 7. were prepared according to the Massart’s method
Aqueous ferrofluid dispersions therefore flocculate [2]. The Fe3O4 precipitate, obtained by alkalizing
in the pH range of 5 to 9 and are stable only under FeCl2 and FeCl3 (Fe2+/Fe3+ = 1/2) aqueous mixture,
highly acidic or basic conditions. On the other hand, was oxidized successively with 2 M HNO3 and
the ZPC of SiO2 is about 2-3 and therefore silica 0.33 M FeNO3 solutions until the Fe2+/Fe3+ ratio in
nanoparticles are negatively charged at pH 7 and the particles was lower than 0.05 and therefore until
consequently their dispersions in biological media magnetite was converted to maghemite. After
would be stable. removing by centrifugation, the particles were
peptized in 2 M HNO3 solution under vigorous
For this reason we investigated the route consisting
stirring in order to create positive surface charges.
of encapsulating preformed maghemite
The acidic precipitate was isolated by decantation
nanoparticles in the ferrofluid state into silica. We
on a magnet, washed in acetone and dispersed in
hoped to obtain core-shell nanoparticles, denoted γ-
pure water at pH ≈ 2.5 in order to obtain an iron
Fe2O3@SiO2, which (i) would form a stable
concentration of 0.125 M.
dispersion in the pH conditions of biological fluids,
(ii) would have sufficiently powerful magnetic γ-Fe2O3@SiO2 synthesis: both types of surfactants
properties and (iii) would have an easy surface were simultaneously used: an ionic one which is
chemistry thanks to the well-known reactivity of dioctyl sulfoccinate, sodium salt (AOT) and a
silica towards coupling agents, such as the nonionic one, which is polyoxyethylene (4) lauryl


The maghemite nanoparticles and therefore the lower the addition of 10 volumes of acetone allowed the number of magnetic cores per silica shell.3/3. the lower the pH value. when mixture to flocculate.5. consequently has migrated into the micelles. Lastly. the BET measurements gave a specific surface area of presence of the acidic ferrofluid catalyzes TEOS 130 m2/g. Characterization techniques: transmission electron microscopy (TEM) experiments were performed c 20 nm d 100 nm with a JEOL 2000 FX operating at an accelerating voltage of 200 kV. nanoparticles were washed with ethanol and chloroform to remove heptane and surfactant. The X-ray diffraction pattern at room hydrolysis. So. After 20 h. but without the drying operation. until the yellow color a 50 nm b vanished. The weight ratio of ferrofluid/TEOS/ammonia used in all experiments was 2. 111 . the temperature (not shown here) is consistent with the main part of TEOS has been pre-hydrolyzed and spinel structure.5. heptane than in aqueous micelles. 2: TEM micrographs of γ-Fe2O3@SiO2 nanoparticles zeta potential titrations were obtained using a vs. tetraethoxysilane by transmission electron microscopy (TEM). It was (TEOS) was added. 2 displays TEM pictures of γ-Fe2O3@SiO2 microemulsions were washed as previously nanoparticles vs. W/O microemulsions were prepared RESULTS AND DISCUSSION by adding the aqueous ferrofluid (whose pH was first adjusted with KOH in the range of 2. Nevertheless. The flocculates were washed with water and centrifuged 50 nm to remove the FeCl3.2/5. The powder was dried at 60°C under vacuum for thermal. c : Zetasizer instrument of Malvern Corporation.5-4. by addition of water.5 M KOH aqueous solution was added on the range. Specific surface areas were measured by nitrogen adsorption (BET e 50 nm f 50 nm method) using a Micromeritics ASAP 2010.5) Shape and size of nanoparticles: the morphology into a stirred solution of Brij®30/AOT (weight of the pristine γ-Fe2O3 nanoparticles was observed ratio 1/2) in heptane. 1). the initial pH of maghemite described. SiO2 hollow spheres synthesis: the flocculates of γ- Fe2O3@SiO2 were leached by 10 M HCl solution in order to dissolve the maghemite cores. Then. the best dispersed the flocculate and mixed in a vortex agitator. In order to obtain the alkaline the value of pH is close to the flocculation pH of 5. a ferrofluids. in the studied pH 0.ether (Brij®30). e : pH 4. 2e). Fig. pH 3. the initial pH of maghemite ferrofluids (a : pH 2. the flocculate was peptized. Samples for TEM were prepared on copper grids coated with a carbon support film (Pelco International) by evaporating a drop of particles dispersion. We supposed that after 15 min. susceptometer MANICS and SQUID 5MPMS. dispersion. respectively). morphology of core-shell particles is less well- defined (Fig.5) and their corresponding silica hollow Magnetic measurements were achieved using a spheres (b. It can be noticed that.%) was added to catalyze the polycondensation of the prehydrolyzed TEOS into silica. TEOS is an organophilic observed that maghemite particles are spherical molecule and therefore is more readily dissolved in with a diameter ranging between 5-10 nm (Fig. magnetic and BET studies. ammonia solution (30 wt. 1: TEM micrograph of γ-Fe2O3 nanoparticles extracted from the ferrofluid (scale bar: 50 nm) γ-Fe2O3@SiO2 aqueous dispersion preparation: Fig. The so-neutralized flocculate was then peptized the alkaline way as for the γ-Fe2O3@SiO2 flocculates. Then. after the aggregates of maghemite form chains and the centrifugation. d and f. The Fig.

remnant magnetization at H = 0. -85 The observed magnetic behavior confirms that γ- Fe2O3 nanoparticles embedded in a silica shell Fig. whereas the γ-Fe2O3 cores in the γ- 112 . M (emu/g) 0. Their specific surface area is 0. The presence of the silica shell 0 100 200 300 400 decreased this value close to the silica ZPC (i.For the particular condition of the ternary system Fe2O3@SiO2 materials remain unaltered until 1273 (water/surfactant/heptane) used in this study. conditions. The size and number of holes seem to volume. Fig.e. the magnetization Mr. BET measurements gave a specific surface area of Magnetic properties: Typical zero field cooled 440 m2/g for core-shell particles displayed on Fig. T K) 2. This feature might allow the dissolution of characteristic of superparamagnetism and is due to the maghemite core. it is well known that Fe2O3@SiO2 (synthesized from the ferrofluid in Fig. known as the 2. The magnetization vs. The absence of coercive -5 hysteresis at 150 K (above the blocking -25 temperature) is characteristic of superparamagnetic -45 γ -Fe2O3@SiO2 particles. 4. depend directly on the size and number of 0. 2b. However. When the field is (synthesized from the ferrofluid in Fig.05 flocculation of the nanoparticles in the pH range 0 from 5 to 9 (Fig. 2a with initial pH of reduced.2 Properties of γ-Fe2O3@SiO2 ferrofluids: Zeta 0. Their diameter is close to that of their parent core-shell blocking for the largest γ-Fe2O3 particles. remain stable until 1273 K and are in agreement Fe2O3 dispersion and γ-Fe2O3@SiO2 dispersion with X-ray diffraction data. temperature in Fig. transform into hematite (α-Fe2O3) at around 673 K. 4: ZFC and FC curves vs.35 maghemite cores. 2a with silica will readily dissolve under highly basic initial pH of 2. obtained by drying the antiferromagnetic α-Fe2O3. the very weak signal Thermal behavior: As already observed for observed was attributed to the transformation of the nanoparticles embedded in silica monoliths [4].15 potential titrations as a function of pH (obtained by adding 0. the maghemite encapsulation by silica. it K (100° step and aging at this temperature for 1 h . temperature of γ- pH higher than 5. 3: Zeta potential titration as a function of pH of the γ. the progressive blocking of the magnetization of smaller and smaller particles when temperature is The electron microscopy pictures of the silica decreasing.25 (480 m2/g versus 440 m2/g). 6 shows the hysteresis loops at 15 K -65 of γ-Fe2O3-silica annealed at different temperature. which is a further proof of and the number of maghemite cores per silica shell. appears that pH is the main parameter that governs X-ray diffraction patterns not shown here).5). data at 15 35 K displays some hysteresis and confirms that the γ- 15 Fe2O3 nanoparticles are ferrimagnetic below the 0 1 2 3 4 5 6 7 8 9 10 11 12 pH blocking temperature. 2d and 2f). Such a behavior is porous. which suggests that the silica shell is highly plotted vs.01 M HNO3 or KOH solutions) allowed to 0. The temperature at which the ZFC and hollow spheres confirm that the maghemite cores the FC curves get separated indicates the onset of have disappeared (Fig. 3). while the particles (in the range of 50 nm).3 H = 50 Oe higher than that of their parent core-shell particles 0. At 1473 K. The field dependent hysteresis loops were measured ζ (mV) at temperatures both below and above the blocking 75 γ -Fe2O3 temperature.1 verify the value of 7 for maghemite ZPC and the 0. the ferrimagnetic γ-Fe2O3 to the canted γ-Fe2O3 nanoparticles. (ZFC) and field cooled magnetization (FC) are 2a. aqueous sol. 5 shows the hysteresis curves at 55 15 K and 150 K. α-Fe2O3 the morphology of the γ-Fe2O3@SiO2 nanoparticles appears only at 1473 K.5). demonstrating the maximum temperature in the ZFC curve can be discriminatory mechanism of the dissolution related to the blocking temperature with the average process.5) and γ-Fe2O3@SiO2 dispersions are stable for a Fig. Fig. remained identical until 1273 K.

8 (magnetic) materials whose synthesis in -1. Jolivet (1998) J Solid State Chem 139:93.5 release the new materials. 1. We have presented a reverse microemulsion Albingre for BET measurements.5 the Japan Society of Powder and Powder H(Oe) Metallurgy. 6: Hysteresis loops at 15 K of γ-Fe2O3@SiO2 J. Teller and M.1 500 1500 2500 3500 (1982) IEEE Trans Magn 17:1247. M (Bohr magneton) 1273 K 1473 K 0. Duguet and J. J.2 Grasset.4 873 K 1 1073 K 0.2 1000 2000 3000 4000 5000 a good correlation between the magnetic core -0. Schütt. Massart -3500 -2500 -1500 -500 -0. Magnetic experiments have shown that maghemite nanoparticles preserve their superparamagnetic properties. Currently. 2 R.0 nanoparticle form is not known. Häfeli.P. ed.0 surface of the silica shells with various alkoxysilane 0.6 150K 0. temperature treatment of solid state chemistry. making them stable in biological fluids. despite being embedded in silica shells. the ferrofluid seems to play an important role in the morphology of the materials and allows to control the number of magnetic cores per silica shell. 0. The authors are deeply grateful to L. Lebraud for technique. These γ-Fe2O3@SiO2 nanoparticles were dispersed in aqueous phase and the ZPC of the new ferrofluid was measured at pH 2. E. Mornet.5. U. It would be stable even during the high Fe2O3@SiO2 nanoparticles. Chanéac and Fig. Maghemite nanoparticles with a silica shell may therefore be readily dispersed in water in the pH range from 5 to 11. ACKNOWLEDGMENTS: The Groupe d’Intérêt Scientifique "Vectorisation in vivo" is gratefully acknowledged for its financial and scientific CONCLUSION AND PERSPECTIVES support. Kyoto and Tokyo.4 15K Concerning the silica hollow nanospheres.8 derivatives and then with molecules of biological and medical interest.2 has demonstrated the possibility to obtain them 0. annealed at different temperatures. Portier (2000) -0. by -0. We are focusing our efforts on their potential applications as (non -0. pp 766-8.3 REFERENCES: Scientific and Clinical 0. No Heated 0. Sellier for carrying out the electron size of a few tens of nanometers. For such H (Oe) applications.0 through a discriminatory dissolution technique with -5000 -4000 -3000 -2000 -1000 0 -0. E. 3 S. New York. Tronc.4 Conference on Ferrites.3 Proceedings of the Eighth International -0. W. the core would be loaded with the precursor and the silica shell could act as a rigid Fig.4 number and the hole number. template.6 magnetic) drug carriers or as nanoreactors for -0. C. -0.1 (eds.2 Applications of Magnetic Microspheres (1997). 0 Zborowski) Plenum Press. and finally would be dissolved under basic conditions to 0. demonstrating the feasibility of the in-temperature X-ray diffraction measurements synthesizing γ-Fe2O3@SiO2 nanoparticles with a and E. our study M (emu/g) 0. 5: Hysteresis loops at 15 K and 150 K of γ. further experiments are in progress to (i) investigate new water/AOT/Brij30®/heptane ratios in order to vary the micelle size and therefore the thickness of the silica shell and (ii) functionalize the 113 . 4 E. The initial pH of microscopy observations. F.