Double-Layer Fatty Acid Nanoparticles as a Multiplatform for Diagnostics and Therapy.

Today, public health is one of the most important challenges in society. Cancer is the leading cause of death, so early diagnosis and localized treatments that minimize side effects are a priority. Magnetic nanoparticles have shown great potential as magnetic resonance imaging contrast agents, detection tags for in vitro biosensing, and mediators of heating in magnetic hyperthermia. One of the critical characteristics of nanoparticles to adjust to the biomedical needs of each application is their polymeric coating. Fatty acid coatings are known to contribute to colloidal stability and good surface crystalline quality. While monolayer coatings make the particles hydrophobic, a fatty acid double-layer renders them hydrophilic, and therefore suitable for use in body fluids. In addition, they provide the particles with functional chemical groups that allow their bioconjugation. This work analyzes three types of self-assembled bilayer fatty acid coatings of superparamagnetic iron oxide nanoparticles: oleic, lauric, and myristic acids. We characterize the particles magnetically and structurally and study their potential for resonance imaging, magnetic hyperthermia, and labeling for biosensing in lateral flow immunoassays. We found that the myristic acid sample reported a large r2 relaxivity, superior to existing iron-based commercial agents. For magnetic hyperthermia, a significant specific absorption rate value was obtained for the oleic sample. Finally, the lauric acid sample showed promising results for nanolabeling.

A Semiproximal Support Vector Machine Approach for Binary Multiple Instance Learning.

We face a binary multiple instance learning (MIL) problem, whose objective is to discriminate between two kinds of point sets: positive and negative. In the MIL terminology, such sets are called bags, and the points inside each bag are called instances. Considering the case with two classes of instances (positive and negative) and inspired by a well-established instance-space support vector machine (SVM) model, we propose to extend to MIL classification the proximal SVM (PSVM) technique that has revealed very effective for supervised learning, especially in terms of computational time. In particular, our approach is based on a new instance-space model that exploits the benefits coming from both SVM (better accuracy) and PSVM (computational efficiency) paradigms. Starting from the standard MIL assumption, such a model is aimed at generating a hyperplane placed in the middle between two parallel hyperplanes: the first one is a proximal hyperplane that clusters the instances of the positive bags, while the second one constitutes a supporting hyperplane for the instances of the negative bags. Numerical results are presented on a set of MIL test data sets drawn from the literature.

Hadron Therapy, Magnetic Nanoparticles and Hyperthermia: A Promising Combined Tool for Pancreatic Cancer Treatment.

A combination of carbon ions/photons irradiation and hyperthermia as a novel therapeutic approach for the in-vitro treatment of pancreatic cancer BxPC3 cells is presented. The radiation doses used are 0-2 Gy for carbon ions and 0-7 Gy for 6 MV photons. Hyperthermia is realized via a standard heating bath, assisted by magnetic fluid hyperthermia (MFH) that utilizes magnetic nanoparticles (MNPs) exposed to an alternating magnetic field of amplitude 19.5 mTesla and frequency 109.8 kHz. Starting from 37 °C, the temperature is gradually increased and the sample is kept at 42 °C for 30 min. For MFH, MNPs with a mean diameter of 19 nm and specific absorption rate of 110 ± 30 W/gFe3o4 coated with a biocompatible ligand to ensure stability in physiological media are used. Irradiation diminishes the clonogenic survival at an extent that depends on the radiation type, and its decrease is amplified both by the MNPs cellular uptake and the hyperthermia protocol. Significant increases in DNA double-strand breaks at 6 h are observed in samples exposed to MNP uptake, treated with 0.75 Gy carbon-ion irradiation and hyperthermia. The proposed experimental protocol, based on the combination of hadron irradiation and hyperthermia, represents a first step towards an innovative clinical option for pancreatic cancer.

Coating Effect on the 1H-NMR Relaxation Properties of Iron Oxide Magnetic Nanoparticles.

We present a 1H Nuclear Magnetic Resonance (NMR) relaxometry experimental investigation of two series of magnetic nanoparticles, constituted of a maghemite core with a mean diameter dTEM = 17 ± 2.5 nm and 8 ± 0.4 nm, respectively, and coated with four different negative polyelectrolytes. A full structural, morpho-dimensional and magnetic characterization was performed by means of Transmission Electron Microscopy, Atomic Force Microscopy and DC magnetometry. The magnetization curves showed that the investigated nanoparticles displayed a different approach to the saturation depending on the coatings, the less steep ones being those of the two samples coated with P(MAA-stat-MAPEG), suggesting the possibility of slightly different local magnetic disorders induced by the presence of the various polyelectrolytes on the particles' surface. For each series, 1H NMR relaxivities were found to depend very slightly on the surface coating. We observed a higher transverse nuclear relaxivity, r2, at all investigated frequencies (10 kHz ≤ νL ≤ 60 MHz) for the larger diameter series, and a very different frequency behavior for the longitudinal nuclear relaxivity, r1, between the two series. In particular, the first one (dTEM = 17 nm) displayed an anomalous increase of r1 toward the lowest frequencies, possibly due to high magnetic anisotropy together with spin disorder effects. The other series (dTEM = 8 nm) displayed a r1 vs. νL behavior that can be described by the Roch's heuristic model. The fitting procedure provided the distance of the minimum approach and the value of the Néel reversal time (τ ≈ 3.5 ÷ 3.9·10-9 s) at room temperature, confirming the superparamagnetic nature of these compounds.

Elongated magnetic nanoparticles with high-aspect ratio: a nuclear relaxation and specific absorption rate investigation.

Medical application of nanotechnology implies the development of nanomaterials capable of being functional in different biological environments. In this sense, elongated nanoparticles (e-MNPs) with high-aspect ratio have demonstrated more effective particle cellular internalization, which is favoured by the increased surface area. This paper makes use of an environmentally friendly hydrothermal method to produce magnetic iron oxide e-MNPs, starting from goethite precursors. At high temperatures (Td) goethite transforms into hematite, which subsequently reduces to magnetite when exposed to a hydrogen atmosphere for a certain time. It is shown that by adjusting Td it is possible to obtain Fe3O4 e-MNPs with partially controlled specific surface area and magnetic properties, attributed to different porosity of the samples. The particles' efficiencies for diagnostic and therapeutic purposes (in magnetic resonance imaging and magnetic fluid hyperthermia, respectively) are very good in terms of clinical standards, some samples showing transversal proton nuclear relaxivity r2 (B0 = 1.33 T) = 340 s-1 mM-1 and specific absorption rate SAR > 370 W g-1 at high field amplitudes (B0 = 55 mT). Direct correlations between the SAR, relaxivity, magnetic properties and porosity of the samples are found, and the physico-chemical processes underneath these correlations are investigated. Our results open the possibility of using very efficient high-aspect ratio elongated nanoparticles with optimized chemico-physical properties for biomedical applications.