Early diagnosis in Alzheimer's disease (AD), prior to the appearance of marked clinical symptoms, is critical to prevent irreversible neuronal damage and neural malfunction that leads to dementia and death. Therefore, there is an urgent need to generate new contrast agents which reveal by a non-invasive method the presence of some of the pathological signs of AD. In the present study we demonstrate for the first time a new nanoconjugate composed of magnetic nanoparticles bound to an anti-ferritin antibody, which has been developed based on the existence of iron deposits and high levels of the ferritin protein present in areas with a high accumulation of amyloid plaques (particularly the subiculum in the hippocampal area) in the brain of a transgenic mouse model with five familial AD mutations. Both in vitro and after intravenous injection, functionalized magnetic nanoparticles were able to recognize and bind specifically to the ferritin protein accumulated in the subiculum area of the AD transgenic mice.

Peer reviewed article authored by (Fernandez Cabada T, Sanchez Lopez de Pablo C, Martinez Serrano A, del Pozo Guerrero F, Serrano Olmedo JJ, Ramos Gomez M). Read article or submit your manuscript for publishing.

The aralar/AGC1 knockout (KO) mouse shows a drastic decrease in brain aspartate and N‐acetylaspartate levels and global hypomyelination, which are attributed to the lack of neuron‐produced NAA used by oligodendrocytes as precursor of myelin lipid synthesis. In addition, these mice have a gradual drop in brain glutamine synthesis. We show here that hypomyelination is more pronounced in gray than in white matter regions. We find a lack of neurofilament‐labelled processes in hypomyelinated fiber tracks from cerebral cortex but not from those of the cerebellar granule cell layer, which correspond to Purkinje neurons. Therefore, the impaired development or degeneration of neuronal processes in cerebral cortex is independent of hypomyelination. An increase in O4‐labelled, immature oligodendrocytes is observed in gray and white matter regions of the aralar KO brain, suggesting a block in maturation compatible with the lack of NAA supplied by neurons. However, no defects in oligodendrocyte maturation were observed in in‐vitro‐cultured mixed astroglial cultures. We conclude that the primary defect of pyramidal neurons in cerebral cortex is possibly associated with a progressive failure in glutamatergic neurotransmission and may be among the main causes of the pathology of aralar/AGC1 deficiency.

For decades now, conventional sinusoidal signals have been exclusively used in magnetic hyperthermia as the only alternating magnetic field waveform to excite magnetic nanoparticles. However, there are no theoretical nor experimental reasons that prevent the use of different waveforms. The only justifiable motive behind using the sinusoidal signal is its availability and the facility to produce it. Following the development of a configurable alternating magnetic field generator, we aim to study the effect of various waveforms on the heat production effectiveness of magnetic nanoparticles, seeking to prove that signals with more significant slope values, such as the trapezoidal and almost-square signals, allow the nanoparticles to reach higher efficiency in heat generation. Furthermore, we seek to point out that the nanoparticle power dissipation is dependent on the waveform’s slope and not only the frequency, magnetic field intensity and the nanoparticle size. The experimental results showed a remarkably higher heat production performance of the nanoparticles when exposed to trapezoidal and almost-square signals than conventional sinusoidal signals. We conclude that the nanoparticles respond better to the trapezoidal and almost-square signals. On the other hand, the experimental results were used to calculate the normalized power dissipation value and prove its dependency on the slope. However, adjustments are necessary to the coil before proceeding with in vitro and in vivo studies to handle the magnetic fields required.

Magnetic resonance imaging is the ideal modality for non-invasive in vivo cell tracking allowing for longitudinal studies over time. Cells labeled with superparamagnetic iron oxide nanoparticles have been shown to induce sufficient contrast for in vivo magnetic resonance imaging enabling the in vivo analysis of the final location of the transplanted cells. For magnetic nanoparticles to be useful, a high internalization efficiency of the particles is required without compromising cell function, as well as validation of the magnetic nanoparticles behaviour inside the cells. In this work, we report the development, optimization and validation of an efficient procedure to label human neural stem cells with commercial nanoparticles in the absence of transfection agents. Magnetic nanoparticles used here do not affect cell viability, cell morphology, cell differentiation or cell cycle dynamics. Moreover, human neural stem cells progeny labeled with magnetic nanoparticles are easily and non-invasively detected long time after transplantation in a rat model of Parkinson’s disease (up to 5 months post-grafting) by magnetic resonance imaging. These findings support the use of commercial MNPs to track cells for short- and mid-term periods after transplantation for studies of brain cell replacement therapy. Nevertheless, long-term MR images should be interpreted with caution due to the possibility that some MNPs may be expelled from the transplanted cells and internalized by host microglial cells.

Magnetic hyperthermia (MHT) is an oncological therapy that uses magnetic nanoparticles (MNPs) to generate localized heat under a low-frequency alternating magnetic field (AMF). Recently, trapezoidal pulsed alternating magnetic fields (TPAMFs) have proven their efficacy in enhancing the efficiency of heating in MHT as compared to the sinusoidal one. Our study aims to compare the TPAMF waveform’s killing effect against the sinusoidal waveform in B16F10 and CT2A cell lines to determine more efficient waveforms in causing cell death. For that purpose, we used MNPs and different AMF waveforms: trapezoidal (TP), almost-square (TS), triangular (TR), and sinusoidal signal (SN). MNPs at 1 and 4 mg/mL did not affect cell viability during treatment. The exposition of B16F10 and CT2A cells to only AMF showed nonsignificant mortality. Hence, the synergetic effect of the AMF and MNPs causes the observed cell death. Among the explored cases, the nonharmonic signals demonstrated better efficacy than the SN one as an MHT treatment. This study has revealed that the application of TP, TS, or TR waveforms is more efficient and has considerable capability to increase cancer cell death compared to the traditional sinusoidal treatment. Overall, we can conclude that the application of nonharmonic signals enhances MHT treatment efficiency against tumor cells.