From Nanothermometry to Bioimaging: Lanthanide-Activated KY3F10 Nanostructures as Biocompatible Multifunctional Tools for Nanomedicine.

Lanthanide-activated fluoride-based nanostructures are extremely interesting multifunctional tools for many modern applications in nanomedicine, e.g., bioimaging, sensing, drug delivery, and photodynamic therapy. Importantly, environmental-friendly preparations using a green chemistry approach, as hydrothermal synthesis route, are nowadays highly desirable to obtain colloidal nanoparticles, directly dispersible in hydrophilic media, as physiological solution. The nanomaterials under investigation are new KY3F10-based citrate-capped core@shell nanostructures activated with several lanthanide ions, namely, Er3+, Yb3+, Nd3+, and Gd3+, prepared as colloidal water dispersions. A new facile microwave-assisted synthesis has been exploited for their preparation, with significant reduction of the reaction times and a fine control of the nanoparticle size. These core@shell multifunctional architectures have been investigated for use as biocompatible and efficient contrast agents for optical, magnetic resonance imaging (MRI) and computerized tomography (CT) techniques. These multifunctional nanostructures are also efficient noninvasive optical nanothermometers. In fact, the lanthanide emission intensities have shown a relevant relative variation as a function of the temperature, in the visible and near-infrared optical ranges, efficiently exploiting ratiometric intensity methods for optical thermometry. Importantly, in contrast with other fluoride hosts, chemical dissolution of KY3F10 citrate-capped nanocrystals in aqueous environment is very limited, of paramount importance for applications in biological fluids. Furthermore, due to the strong paramagnetic properties of lanthanides (e.g., Gd3+), and X-ray absorption of both yttrium and lanthanides, the nanostructures under investigation are extremely useful for MRI and CT imaging. Biocompatibility studies of the nanomaterials have revealed very low cytotoxicity in dfferent human cell lines. All these features point to a successful use of these fluoride-based core@shell nanoarchitectures for simultaneous diagnostics and temperature sensing, ensuring an excellent biocompatibility.

Doped Ferrite Nanoparticles Exhibiting Self-Regulating Temperature as Magnetic Fluid Hyperthermia Antitumoral Agents, with Diagnostic Capability in Magnetic Resonance Imaging and Magnetic Particle Imaging.

This paper reports a comprehensive investigation of a magnetic nanoparticle (MNP), named M55, which belongs to a class of innovative doped ferrite nanomaterials, characterized by a self-limiting temperature. M55 is obtained from M48, an MNP previously described by our group, by implementing an additional purification step in the synthesis. M55, after citrate and glucose coating, is named G-M55. The present study aimed to demonstrate the properties of G-M55 as a diagnostic contrast agent for MRI and magnetic particle imaging (MPI), and as an antitumoral agent in magnetic fluid hyperthermia (MFH). Similar specific absorption rate values were obtained by standard MFH and by an MPI apparatus. This result is of interest in relation to the application of localized MFH by MPI apparatus. We demonstrated the biocompatibility of G-M55 in a triple-negative human breast cancer line (MDA-MB-231), and its efficacy as an MFH agent in the same cell line. We also demonstrated the efficacy of MFH treatment with G-M55 in an experimental model of breast cancer. Overall, our results pave the way for the clinical application of G-M55 as an MFH agent in breast cancer therapy, allowing not only efficient treatment by both standard MFH apparatus and MPI but also temperature monitoring.

Beneficial and Sexually Dimorphic Response to Combined HDAC Inhibitor Valproate and AMPK/SIRT1 Pathway Activator Resveratrol in the Treatment of ALS Mice.

Amyotrophic lateral sclerosis (ALS) is a fatal adult-onset neurodegenerative disorder. There is no cure and current treatments fail to slow the progression of the disease. Epigenetic modulation in the acetylation state of NF-kB RelA and the histone 3 (H3) protein, involved in the development of neurodegeneration, is a drugable target for the class-I histone deacetylases (HDAC) inhibitors, entinostat or valproate, and the AMP-activated kinase (AMPK)-sirtuin 1 pathway activator, resveratrol. In this study, we demonstrated that the combination of valproate and resveratrol can restore the normal acetylation state of RelA in the SOD1(G93A) murine model of ALS, in order to obtain the neuroprotective form of NF-kB. We also investigated the sexually dimorphic development of the disease, as well as the sex-sensibility to the treatment administered. We showed that the combined drugs, which rescued AMPK activation, RelA and the histone 3 acetylation state, reduced the motor deficit and the disease pathology associated with motor neuron loss and microglial reactivity, Brain-Derived Neurotrophic Factor (BDNF) and B-cell lymphoma-extra large (Bcl-xL) level decline. Specifically, vehicle-administered males showed earlier onset and slower progression of the disease when compared to females. The treatment, administered at 50 days of life, postponed the time of onset in the male by 22 days, but not in a significant way in females. Nevertheless, in females, the drugs significantly reduced symptom severity of the later phase of the disease and prolonged the mice's survival. Only minor beneficial effects were produced in the latter stage in males. Overall, this study shows a beneficial and sexually dimorphic response to valproate and resveratrol treatment in ALS mice.