RESUMEN
Ultra-small dextran coated maghemite nanoparticles are synthesized via a low temperature modified co-precipitation method. A monoethylene glycol/water solution of 1:1 molar ratios and a fixed apparatus is used at a constant temperature of 5-10 degrees C. The growth of nanoparticles is prohibited due to low temperature synthesis and differs from usual thermal decomposition methods via Ostwald ripening. Strict temperature control and reaction timing of less than 20 minutes are essential to maintain narrow distribution in particle size. These nanoparticles are water-dispersible and biocompatible by capping with polyethylene glycol ligands. The aqueous suspensions are tested for cytotoxic activity on normal human skin fibroblasts. There is no reduction of the cells' viability at any concentration tested, the highest being 1% v/v of the suspension in culture medium, corresponding to the highest concentrations to be administered in vivo. Initial comparison with a T1 MRI contrast agent in sale shows that maghemite nanoparticles exhibit high r1 and r2 relaxivities in MRI tomography and strong contrast in computed tomography, demonstrating that these nanoparticles can be efficient T1, T2 and CT contrast agents.
Asunto(s)
Medios de Contraste/química , Dextranos/química , Imagen por Resonancia Magnética/métodos , Nanopartículas de Magnetita/química , Tomografía Computarizada por Rayos X/métodos , Línea Celular , Supervivencia Celular/efectos de los fármacos , Precipitación Química , Frío , Medios de Contraste/toxicidad , Dextranos/toxicidad , Humanos , Nanopartículas de Magnetita/toxicidad , Fantasmas de ImagenRESUMEN
One of the most significant challenges implementing colloidal magnetic nanoparticles in medicine is the efficient heating of microliter quantities by applying a low frequency alternating magnetic field. The ultimate goal is to accomplish nonsurgically the treatment of millimeter size tumors. Here, we demonstrate the synthesis, characterization, and the in vitro as well as in vivo efficiency of a dextran coated maghemite (gamma-Fe(2)O(3)) ferrofluid with an exceptional response to magnetic heating. The difference to previous synthetic attempts is the high charge of the dextran coating, which according to our study maintains the colloidal stability and good dispersion of the ferrofluid during the magnetic heating stage. Specifically, in vitro 2 mul of the ferrofluid gives an outstanding temperature rise of 33 degrees C within 10 min, while in vivo treatment, by infusing 150 mul of the ferrofluid in animal model (rat) glioma tumors, causes an impressive cancer tissue dissolution.
RESUMEN
The influence of coating on interparticle interactions in ferrofluids has been investigated using various techniques such as Mossbauer spectroscopy, magnetometry, transmission electron microscopy, photon correlation spectroscopy, X-ray diffraction, X-ray photoelectron, and resonance micro-Raman spectroscopy. Aging and spin-glass-like behavior was investigated in frozen ferrofluids of various concentrations from dense, initial value of 40 mg of coated nanoparticles per 1 mL of water, to dilute 1:10 (4 mg/mL). The as-prepared nanoparticles, core size 7-8 nm, were subsequently coated with a gummic acid corona of 20 nm thickness, which was observed to prevent agglomeration and to delay aggregation even in dense ferrofluids. The resulting separation of magnetic cores due to the coating eliminated all magnetic interparticle interaction mechanisms, such as exchange and dipoledipole, thus ensuring no aging effects of the magnetic particle system, as manifested in particle agglomeration and precipitation.