Alejandro G. Roca

Progress in the preparation of magnetic nanoparticles for applications in biomedicine

This review summarizes recent advances in synthesis routes for quickly and reliably making and functionalizing magnetic nanoparticles for applications in biomedicine. We put special emphasis on describing synthetic strategies that result in the production of nanosized materials with well-defined physical and crystallochemical characteristics as well as colloidal and magnetic properties. Rather than grouping the information according to the synthetic route, we have described methods to prepare water-dispersible equiaxial magnetic nanoparticles with sizes below about 10 nm, sizes between 10 and 30 nm and sizes around the monodomain–multidomain magnetic transition. We have also described some recent examples reporting the preparation of anisometric nanoparticles as well as methods to prepare magnetic nanosized materials other than iron oxide ferrites, for example Co and Mn ferrite, FePt and manganites. Finally, we have described examples of the preparation of multicomponent systems with purely inorganic or organic–inorganic characteristics.

Structural and magnetic properties of uniform magnetite nanoparticles prepared by high temperature decomposition of organic precursors

Magnetite nanoparticles (Fe3O4) of three different sizes below the limit for single domain magnetic behaviour have been obtained by thermal decomposition of an iron precursor in an organic medium in the presence of a surfactant. Good agreement between mean particle size obtained by TEM, crystal size calculated from x-ray diffraction and magnetic diameter calculated from magnetization curves measured at room temperature shows that the samples consist of uniform, crystalline and isolated magnetite nanoparticles with sizes between 5 and 11 nm. High saturation magnetization and high initial susceptibility values have been found, the latter decreasing as the particle size decreases. The main contribution to the anisotropy is magnetocrystalline and shape anisotropy, since surface anisotropy is suppressed by the oleic acid molecules which are covalently bonded to the nanoparticle surface.

The influence of surface functionalization on the enhanced internalization of magnetic nanoparticles in cancer cells

The internalization and biocompatibility of iron oxide nanoparticles surface functionalized with four differently charged carbohydrates have been tested in the human cervical carcinoma cell line (HeLa). Neutral, positive, and negative iron oxide nanoparticles were obtained by coating with dextran, aminodextran, heparin, and dimercaptosuccinic acid, resulting in colloidal suspensions stable at pH 7 with similar aggregate size. No intracellular uptake was detected in cells incubated with neutral charged nanoparticles, while negative particles showed different behaviour depending on the nature of the coating. Thus, dimercaptosuccinic-coated nanoparticles showed low cellular uptake with non-toxic effects, while heparin-coated particles showed cellular uptake only at high nanoparticle concentrations and induced abnormal mitotic spindle configurations. Finally, cationic magnetic nanoparticles show excellent properties for possible in vivo biomedical applications such as cell tracking by magnetic resonance imaging (MRI) and cancer treatment by hyperthermia: (i) they enter into cells with high effectiveness, and are localized in endosomes; (ii) they can be easily detected inside cells by optical microscopy, (iii) they are retained for relatively long periods of time, and (iv) they do not induce any cytotoxicity.

Uniform and water stable magnetite nanoparticles with diameters around the monodomain–multidomain limit

A direct method for the preparation of uniform magnetite nanoparticles with sizes around 30?nm and stable in aqueous media at pH 7 has been developed. This method is based on the precipitation of an iron (II) salt (FeSO4) in the presence of a base (NaOH) and a mild oxidant (KNO3). Reaction rate seems to be controlled by the iron salt concentration and the presence of ethanol in the media. Thus lower iron concentration and a water/ethanol ratio equal to one lead to the formation of the smallest particles, 30?nm in diameter. Colloidal suspensions of these particles were directly obtained by simple ultrasonic treatment of the powders leading to very stable ferrofluids at pH 7. Sulphate anions present at the particle surface seem to be responsible for the colloidal stability, providing a biocompatible character to the suspensions. The structural, morphological and magnetic characterization of the nanoparticles is also described and suggests that the smallest particles have a diameter close to the limit between monodomain?multidomain magnetic structure, which could account for the high powder absorption of magnetic fields. According to this calorimetric experiments resulted in specific power absorption rates of ca 80?95?W?g?1, which are among the highest values reported in the literature and make these nanoparticles very interesting for hyperthermia.

Effect of Nanoparticle and Aggregate Size on the Relaxometric Properties of MR Contrast Agents Based on High Quality Magnetite Nanoparticles

Colloidal dispersions of monodispersed and high-crystalline magnetite nanoparticles have been used to establish a relationship between magnetic properties and magnetic resonance (MR) relaxometric parameters in vitro. Magnetite nanoparticles with diameters between 4 and 14 nm were synthesized by thermal decomposition of Fe(acac)3 in different organic solvents and transformed to hydrophilic by changing oleic acid for dimercaptosuccinic acid (DMSA). A final treatment in alkaline water was critical to make the suspension stable at pH 7 with xi-potential values of -45 mV and hydrodynamic sizes as low as 50 nm. Samples showed superparamagnetic behavior at room temperature, which is an important parameter for biomedical applications. Susceptibility increased with both particle and aggregate size, and for particles larger than 9 nm, the aggregate size was the key factor controlling the susceptibility. Relaxivity values followed the same trend as the suspension susceptibilities, indicating that the aggregate size is an important factor above a certain particle size governing the proton relaxation times. The highest relaxivity value, r2=317 s(-1) mM(-1), much higher than those for commercial contrast agents with similar hydrodynamic size, was obtained for a suspension consisting of 9 nm particles and 70 nm of hydrodynamic size, and it was assigned to the higher particle crystallinity in comparison to particles prepared by coprecipitation. Therefore, it can be concluded that in addition to the sample crystallinity, both particle size and aggregate size should be considered in order to explain the magnetic and relaxivity values of a suspension.

Magnetic nanoparticles with bulklike properties (invited)

The magnetic behavior of Fe3� xO4 nanoparticles synthesized by either high-temperature decomposition of an organic iron precursor or low-temperature coprecipitation in aqueous conditions is compared. Transmission electron microscopy, x-ray absorption spectroscopy, x-ray magnetic circular dichroism, and magnetization measurements show that nanoparticles synthesized by thermal decomposition display high crystal quality and bulklike magnetic and electronic properties, while nanoparticles synthesized by coprecipitation show much poorer crystallinity and particlelike phenomenology, including reduced magnetization, high closure fields, and shifted hysteresis loops. The key role of the crystal quality is thus suggested, because particlelike behavior for particles larger than about 5 nm is observed only when the particles are structurally defective. These conclusions are supported by Monte Carlo simulations. It is also shown that thermal decomposition is capable of producing nanoparticles that, after further stabilization in physiological conditions, are suitable for biomedical applications such as magnetic resonance imaging or biodistribution studies. V C 2011 American Institute of Physics. [doi:10.1063/1.3559504]

Magnetite nanoparticles with no surface spin canting

Surface spin canting has been studied for high quality magnetite nanoparticles in terms of size and shape uniformity. Particles were prepared by thermal decomposition of organic precursors in organic media and in the presence of oleic acid. Results are compared to spin canting effect for magnetic iron oxide nanoparticles of similar size prepared by coprecipitation and subsequently coated with silica. Magnetic characterization and Mossbauer spectroscopy at low temperature and in the presence of a magnetic field have been used in this study. Transmission electron microscopy images and x-ray diffractograms show that iron oxide nanoparticles synthesized by thermal decomposition are more uniform than those prepared by coprecipitation, and they have higher crystal order. Magnetic measurements show superparamagnetic behavior for both samples at room temperature but particles synthesized by thermal decomposition shows higher saturation magnetization and lower coercivity at low temperature. The imaginary part of t...

Liver and brain imaging through dimercaptosuccinic acid-coated iron oxide nanoparticles

BACKGROUND & AIM Uptake, cytotoxicity and interaction of improved superparamagnetic iron oxide nanoparticles were studied in cells, tissues and organs after single and multiple exposures. MATERIAL & METHOD We prepared dimercaptosuccinic acid-coated iron oxide nanoparticles by thermal decomposition in organic medium, resulting in aqueous suspensions with a small hydrodynamic size (< 100 nm), high saturation magnetization and susceptibility, high nuclear magnetic resonance contrast and low cytotoxicity. RESULTS In vitro and in vivo behavior showed that these nanoparticles are efficient carriers for drug delivery to the liver and brain that can be combined with MRI detection.

Synthesis of Monodispersed Magnetite Particles From Different Organometallic Precursors

Magnetite (Fe3O4) nanoparticles with very narrow particle size distribution can be obtained by decomposition of an organometallic compound in the presence of oleic acid. It has been shown that the carboxylic acid catalyzes the reaction leading to decreased decomposition temperatures and, consequently, as the surfactant concentration increases, smaller particles are formed. Precursors such as Fe(CO)5, iron acetylacetonate, and iron-oleate complexes, previously formed from an iron salt, have been used for the preparation of magnetite particles. Although the particles are magnetite in all cases, the size, shape, and distribution of nanoparticles differ depending on the precursor and consequently the samples show different magnetic behavior. Besides, a different mechanism of formation of the nanoparticles is expected and related to the decomposition rate of the precursor

Cytokine adsorption/release on uniform magnetic nanoparticles for localized drug delivery.

Attachment of cytokines to magnetic nanoparticles has been developed as a system for controlled local drug release in cancer therapy. We studied the adsorption/release of murine interferon gamma (IFN-gamma) on negatively charged magnetic nanoparticles prepared by three different methods, including coprecipitation, decomposition in organic media, and laser pyrolysis. To facilitate IFN-gamma adsorption, magnetic nanoparticles were surface modified by distinct molecules to achieve high negative charge at pH 7, maintaining small aggregate size and stability in biological media. We analyzed carboxylate-based coatings and studied the colloidal properties of the resulting dispersions. Finally, we incubated the magnetic dispersions with IFN-gamma and determined optimal conditions for protein adsorption onto the particles, as well as the release capacity at different pH and as a function of time. Particles prepared by decomposition in organic media and further modified with dimercaptosuccinic acid showed the most efficient adsorption/release capacity. IFN-gamma adsorbed on these nanoparticles would allow concentration of this protein or other biomolecules at specific sites for treatment of cancer or other diseases.