Nanomaterials for Biomedical Applications: Magnetic Hyperthermia and Magnetofection

FRANCISCO H. SÁNCHEZ

Buenos Aires

Workshop; Latin American Workshop on Magnetism and Magnetic Materials; 2013

TANDAR-CNEA, UBA

Nanomaterials provide a source for new potential applications in a diversity of technologyfields, as for example energy, environment, and health. They constitute also a benchmark forstudying basic properties which emerge from the nanoscale.For biomedical applications like magnetic hyperthermia, magnetofection, magneticseparation and drug delivery, the response of nanoparticles (NPs) and NP-based composites toapplied magnetic fields is of crucial importance. This response involves forces on the NPs as wellas their magnetization behavior, which are strongly influenced by the NPs single domain state, bythe NPs moment relaxation mechanisms, and by dipolar interactions among NPs. Therefore, it isnecessary to perform detailed experimental studies on especially designed nanomaterials in order toadvance in the development of these applications.In the case of NPs and ferrofluids for magnetic hyperthermia it is important to recognizewhether the power absorption by NPs from a radiofrequency (RF) field involves Néel or Brownrelaxation mechanisms, to quantify the NPs specific absorption rate (SAR) and to correlate thisfigure of merit with other NPs structural and magnetic properties. As examples of this type ofresearch recent experiments performed in collaboration are discussed. Aqueous ferrofluids made ofZn doped magnetite NPs of different compositions and sizes, obtained by chemical coprecipitation,were prepared. A linear dependence of SAR on ferrofluid concentration c and on squared-RF fieldamplitude H02 was observed, for c £ 12 kg/m3 and H0 £ 41 kA/m, respectively. Relaxation times atRT were obtained from SAR experiments and found to be in good agreement with those calculatedfor Néel or Brown mechanisms and with those retrieved from Mössbauer measurements. In theferrofluid samples, at RT and 260 kHz, it was found that relaxation of the NP moment occurs viathe Néel mechanism for sizes below 18 nm and via the Brown one for larger sizes, and that SARvalues of up to 370 W/g are achievable for selected compositions and NP sizes (e.g. 16 nmZn0.1Fe2.9O4 NPs). Furthermore, Mössbauer, XRD and XAS experiments confirmed that Zn entersselectively at the spinel tetrahedral site, a fact which explains the enhancement of NP net magneticmoment observed for small Zn additions. Examples of coating induced phenomena will bepresented for the case of magnetite NPs funtionalized with citric acid. Coating of NPs with proteins,polymers and carboxylates, usually performed to improve ferrofluid stability and biocompatibility,modifies NPs heat dissipation ability. This effect is discussed in connection with experimentalsynthesis parameters and on the basis of TEM, PALS, magnetization and SAR results. As aconsequence of coating the NP hydrodynamic size grew, which increased the relaxation timeassociated with the Brown mechanism. Coating also gave rise to steric repulsion reducing dipolarinteractions among particles which in turns affected the Néel relaxation mechanism. Finally, itinfluenced the magnetic order at the NP near surface region, changing its effective saturationmagnetization MS and therefore affecting SAR which scales with MS2.Preliminary results of in vitro magnetofection experiments performed in collaboration withDr. R. Goya (INIBIOLP-CONICET) will be also included in this presentation. Magnetofectionstands for magnetically assisted gene transfer, which opens the way to an innovative therapeuticapproach. In this preliminary research magnetic field applicators for in vitro experiments were builtand fully characterized. The recombinant adenoviral vector termed RAd-GFP, which harbors thegene for green fluorescent protein (GFP), was complexed with polymer coated magnetite NPs, andthe complex was incubated with B-92 glial cell cultures in the presence of an external magneticfield. In order to study and quantify the effect of the applied field on transduction efficiency,magnetofection was plotted as a function of the distance between the field applicator and the cellmonolayer. After estimating the magnetic force on the NP/virus complexes an empirical correlationbetween this quantity and transfection efficiency was observed.