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.

NMR as evaluation strategy for cellular uptake of nanoparticles.

Advanced nanostructured materials, such as gold nanoparticles, magnetic nanoparticles, and multifunctional materials, are nowadays used in many state-of-the-art biomedical application. However, although the engineering in this field is very advanced, there remain some fundamental problems involving the interaction mechanisms between nanostructures and cells or tissues. Here we show the potential of (1)H NMR in the investigation of the uptake of two different kinds of nanostructures, that is, maghemite and gold nanoparticles, and of a chemotherapy drug (Temozolomide) in glioblastoma tumor cells. The proposed experimental protocol provides a new way to investigate the general problem of cellular uptake for a variety of biocompatible nanostructures and drugs.

Magnetism and spin dynamics of novel encapsulated iron oxide superparamagnetic nanoparticles.

Encapsulated Fe3O4 nanoparticles of average diameters d = 12 nm are obtained by coprecipitation, in the presence of 2-methoxyethanol hemiester of poly(maleic anhydride-alt-butyl vinyl ether) 5% grafted with poly(ethylene glycol) (VP-MAG nanoparticles). A complete characterization of nude and encapsulated nanoparticles through structural techniques (namely XRD, TEM, SEM), Raman spectroscopy and magnetic measurements has been performed. These nanoparticles compared with commercial compounds (ENDOREM®) present superparamagnetic behavior and nuclear relaxivities that make them promising as magnetic resonance imaging (MRI) contrast agents (CAs). We found that our nanostructures exhibit r2 relaxivity higher than those of commercial CAs over the whole frequency range. The MRI efficiency of our samples was related to their microstructural and magnetic properties.

Probing α-relaxation with nuclear magnetic resonance echo decay and relaxation: a study on nitrile butadiene rubber.

One dimensional (1)H NMR measurements have been performed to probe slow molecular motions in nitrile butadiene rubber (NBR) around its calorimetric glass transition temperature Tg. The purpose is to show how software aided data analysis can extract meaningful dynamical data from these measurements. Spin-lattice relaxation time, free induction decay (FID) and magic sandwich echo (MSE) measurements have been carried out at different values of the static field, as a function of temperature. It has been evidenced how the efficiency of the MSE signal in reconstructing the original FID exhibits a sudden minimum at a given temperature, with a slight dependence from the measuring frequency. Computer simulations performed with the software SPINEVOLUTION have shown that the minimum in the efficiency reconstruction of the MSE signal corresponds to the average motional frequency taking a value around the inter-proton coupling. The FID signals have been fitted with a truncated form of a newly derived exact correlation function for the transverse magnetization of a dipolar interacting spin pair, which allows one to avoid the restriction of the stationary and Gaussian approximations. A direct estimate of the conformational dynamics on approaching the Tg is obtained, and the results are in agreement with the analysis performed via the MSE reconstruction efficiency. The occurrence of a wide distribution of correlation frequencies for the chains motion, with a Vogel-Fulcher type temperature dependence, is addressed. A route for a fruitful study of the dynamics accompanying the glass transition by a variety of NMR measurements is thus proposed.

Hybrid iron oxide-copolymer micelles and vesicles as contrast agents for MRI: impact of the nanostructure on the relaxometric properties.

Magnetic resonance imaging (MRI) is at the forefront of non-invasive medical imaging techniques. It provides good spatial and temporal resolution that can be further improved by the use of contrast agents (CAs), providing a valuable tool for diagnostic purposes. Ultrasmall superparamagnetic iron oxide (USPIO) nanoparticles are attractive MRI contrast agents due to their negative (T2) contrast enhancement capability and biocompatibility. Clusters of USPIOs with polymer material are of particular interest since they can sustain additional functionalities like drug delivery and targeting. Aiming to establish a relationship between the morphology of the clusters and their efficacy as MRI contrast agents (relaxometric properties), we prepared - using three different maghemite (γ-Fe2O3) USPIO diameters - a series of hybrid copolymer/iron oxide CAs presenting two different geometries (micellar or vesicular). The NMR relaxometry profiles confirmed the nature of the physical mechanisms inducing the increase of nuclear relaxation rates at low (magnetic anisotropy) and high (Curie relaxation) magnetic fields. A heuristic model, first proposed by Roch, Muller, Gillis, and Brooks, allowed the fitting of the whole longitudinal relaxivity r1(ν) profile, for samples with different magnetic core sizes. We show that both types of clusters exhibit transverse relaxivity (r2) values comparable to or higher than those of common contrast agents, over the whole tested frequency range. Moreover, in-depth analysis revealed substantially a linear relationship between r2 and the number of encapsulated USPIOs divided by the diameter of the clusters (NUSPIO/DH), for each USPIO size. The cluster structure (i.e. micelle or vesicle) appeared to have a mild influence on the transverse relaxivity value. Indeed, the r2 value was mainly governed by the individual size of the USPIOs, correlated with both the cluster external diameter and the magnetic material volume fraction.

New frontiers for astrocytic tumours.

Glioblastoma multiforme, the most common type of primary brain tumour, remains an unsolved clinical problem. A great deal of work has been done in an effort to understand the biology and genetics of glioblastoma multiforme, but clinically effective treatments remain elusive. It is well known that malignant gliomas develop resistance to chemo- and radiotherapy. In this review we evaluated the literature data regarding therapeutic progress for the treatment of astrocytic tumours, focusing our attention on new frontiers for glioblastoma. The research studies performed in in vitro and in vivo models show that the application of hyperthermia using magnetic nanoparticles is safe and could be a promising tool in the treatment of glioblastoma patients. Our efforts are focused towards new fields of research, for example nanomedicine and the study of the uptake and cytotoxic effects of magnetic nanoparticles. The improvement of the quality of life of patients, by increasing their survival rate is the best result to be pursued, since these tumours are considered as ineradicable.

One-pot synthesis and characterization of size-controlled bimagnetic FePt-iron oxide heterodimer nanocrystals.

A one-pot, two-step colloidal strategy to prepare bimagnetic hybrid nanocrystals (HNCs), comprising size-tuned fcc FePt and inverse spinel cubic iron oxide domains epitaxially arranged in a heterodimer configuration, is described. The HNCs have been synthesized in a unique surfactant environment by temperature-driven sequential reactions, involving the homogeneous nucleation of FePt seeds and the subsequent heterogeneous growth of iron oxide. This self-regulated mechanism offers high versatility in the control of the geometric features of the resulting heterostructures, circumventing the use of more elaborate seeded growth techniques. It has been found that, as a consequence of the exchange coupling between the two materials, the HNCs exhibit tunable single-phase-like magnetic behavior, distinct from that of their individual components. In addition, the potential of the heterodimers as effective contrast agents for magnetic resonance imaging techniques has been examined.