Chemical engineering of cationic distribution in spinel ferrite nanoparticles: the effect on the magnetic properties.

A set of ∼9 nm CoFe2O4 nanoparticles substituted with Zn2+ and Ni2+ was prepared by thermal decomposition of metallic acetylacetonate precursors to correlate the effects of replacement of Co2+ with the resulting magnetic properties. Due to the distinct selectivity of these cations for the spinel ferrite crystal sites, we show that it is possible to tailor the magnetic anisotropy, saturation magnetization, and interparticle interactions of the nanoparticles during the synthesis stage. This approach unlocks new possibilities for enhancing the performance of spinel ferrite nanoparticles in specific applications. Particularly, our study shows that the replacement of Co2+ by 48% of Zn2+ ions led to an increase in saturation magnetization of approximately 40% from ∼103 A m2 kg-1 to ∼143 A m2 kg-1, whereas the addition of Ni2+ at a similar percentage led to an ∼30% decrease in saturation magnetization to 68-72 A m2 kg-1. The results of calculations based on the two-sublattice Néel model of magnetization match the experimental findings, demonstrating the model's effectiveness in the strategic design of spinel ferrite nanoparticles with targeted magnetic properties through doping/inversion degree engineering.

Magnetic implants in vivo guiding sorafenib liver delivery by superparamagnetic solid lipid nanoparticles.

HYPOTHESIS: Solid lipid nanoparticles (SLNs), co-encapsulating superparamagnetic iron oxide nanoparticles and sorafenib, have been exploited for magnetic-guided drug delivery to the liver. Two different magnetic configurations, both comprising two small magnets, were under-skin implanted to investigate the effect of the magnetic field topology on the magnetic SLNP accumulation in liver tissues. A preliminary simulation analysis was performed to predict the magnetic field topography for each tested configuration. EXPERIMENTS: SLNs were prepared using a hot homogenization approach and characterized using complementary techniques. Their in vitro biological behavior was assessed in HepG-2 liver cancer cells; wild-type mice were used for the in vivo study. The magnet configuration that resulted in a higher magnetic targeting efficiency was investigated by evaluating the iron content in homogenated murine liver tissues. FINDINGS: SLNs, characterized by an average size smaller than 200 nm, retained their superparamagnetic behavior and relevant molecular resonance imaging properties as negative contrast agents. The evaluation of iron accumulation in the liver tissues was consistent with the magnetic induction profile of each magnet configuration, concurring with the results predicted by simulation analysis and obtained by measurements in living mice.

Cholesterol Hinders the Passive Uptake of Amphiphilic Nanoparticles into Fluid Lipid Membranes.

Plasma membranes represent pharmacokinetic barriers for the passive transport of site-specific drugs within cells. When engineered nanoparticles (NPs) are considered as transmembrane drug carriers, the plasma membrane composition can affect passive NP internalization in many ways. Among these, cholesterol-regulated membrane fluidity is probably one of the most biologically relevant. Herein, we consider small (2-5 nm in core diameter) amphiphilic gold NPs capable of spontaneously and nondisruptively entering the lipid bilayer of plasma membranes. We study their incorporation into model 1,2-dioleoyl-sn-glycero-3-phosphocholine membranes with increasing cholesterol content. We combine dissipative quartz crystal microbalance experiments, atomic force microscopy, and molecular dynamics simulations to show that membrane cholesterol, at biologically relevant concentrations, hinders the molecular mechanism for passive NP penetration within fluid bilayers, resulting in a dramatic reduction in the amount of NP incorporated.

Non-disruptive uptake of anionic and cationic gold nanoparticles in neutral zwitterionic membranes.

The potential toxicity of ligand-protected nanoparticles (NPs) on biological targets is crucial for their clinical translation. A number of studies are aimed at investigating the molecular mechanisms shaping the interactions between synthetic NPs and neutral plasma membranes. The role played by the NP surface charge is still widely debated. We compare, via liposome leakage assays, the perturbation induced by the penetration of sub-6 nm anionic and cationic Au NPs into model neutral lipid membranes composed of the zwitterionic 1-palmitoyl-2-oleoyl-sn-glycero-3-phosphocholine (POPC). Our charged Au NPs are functionalized by a mixture of the apolar 1-octanethiol and a ω-charged thiol which is either the anionic 11-mercapto-1-undecanesulfonate or the cationic (11-mercaptoundecyl)-N,N,N-trimethylammonium. In both cases, the NP uptake in the bilayer is confirmed by quartz crystal microbalance investigations. Our leakage assays show that both negatively and positively charged Au NPs do not induce significant membrane damage on POPC liposomes when penetrating into the bilayer. By means of molecular dynamics simulations, we show that the energy barrier for membrane penetration is the same for both NPs. These results suggest that the sign of the NP surface charge, per se, does not imply different physicochemical mechanisms of interaction with zwitterionic lipid membranes.

Amphiphilic gold nanoparticles perturb phase separation in multidomain lipid membranes.

Amphiphilic gold nanoparticles with diameters in the 2-4 nm range are promising as theranostic agents thanks to their spontaneous translocation through cell membranes. This study addresses the effects that these nanoparticles may have on a distinct feature of plasma membranes: lipid lateral phase separation. Atomic force microscopy, quartz crystal microbalance, and molecular dynamics are combined to study the interaction between model neuronal membranes, which spontaneously form ordered and disordered lipid domains, and amphiphilic gold nanoparticles having negatively charged surface functionalization. Nanoparticles are found to interact with the bilayer and form bilayer-embedded ordered aggregates. Nanoparticles also suppress lipid phase separation, in a concentration-dependent fashion. A general, yet simple thermodynamic model is developed to show that the change of lipid-lipid enthalpy is the dominant driving force towards the nanoparticle-induced destabilization of phase separation.

Gold-Speckled SPION@SiO2 Nanoparticles Decorated with Thiocarbohydrates for ASGPR1 Targeting: Towards HCC Dual Mode Imaging Potential Applications.

Efforts are made to perform an early and accurate detection of hepatocellular carcinoma (HCC) by simultaneous exploiting multiple clinically non-invasive imaging modalities. Original nanostructures derived from the combination of different inorganic domains can be used as efficient contrast agents in multimodal imaging. Superparamagnetic iron oxide nanoparticles (SPIONs) and Au nanoparticles (NPs) possess well-established contrasting features in magnetic resonance imaging (MRI) and X-ray computed tomography (CT), respectively. HCC can be targeted by using specific carbohydrates able to recognize asialoglycoprotein receptor 1 (ASGPR1) overexpressed in hepatocytes. Here, two different thiocarbohydrate ligands were purposely designed and alternatively conjugated to the surface of Au-speckled silica-coated SPIONs NPs, to achieve two original nanostructures that could be potentially used for dual mode targeted imaging of HCC. The results indicated that the two thiocarbohydrate decorated nanostructures possess convenient plasmonic/superparamagnetic properties, well-controlled size and morphology and good selectivity for targeting ASGPR1 receptor.

Cyclodextrin-Based Organic Radical Contrast Agents for in†vivo Imaging of Gliomas.

Cyclodextrins (CDs), a class of cyclic oligosaccharides formed by α-(1,4) linked glucopyranose units, were functionalized with (2,2,6,6-tetramethylpiperidin-1-yl)oxyl (TEMPO) radicals to prepare water soluble supramolecular organic radical contrast agents (ORCAs) for the in vivo detection of glioma tumor in animal models. A first set of molecules (CDn1, n=6,7,8 is the number of both TEMPO and glucopyranose units) was studied by superconducting quantum interference devices (SQUID) magnetometry in order to define the role of the CD macrocycle on the effective magnetic moment (µeff ). The µeff value increased from 3.982 µB (CD61) to 4.522 µB (CD81) but was limited by intramolecular antiferromagnetic (AF) interactions. A set of water-soluble ORCAs (CDn8, n=6,7,8) was prepared by a sequence of thiol-ene and Cu(I)-catalyzed alkyne-azide "click" reactions. Their 1 H water relaxivities r1 of these ORCAs were between 0.739 mM-1 s-1 (CD68) to 1.047 mM-1 s-1 (CD88) in D2 O/H2 O 9 : 1 (v : v) at 300 K. One of them (CD78) was tested on glioma-bearing rats with reduced side effects and good relaxivity in vivo.

Magnetic calcium phosphates nanocomposites for the intracellular hyperthermia of cancers of bone and brain.

Aim: Magnetic hyperthermia is limited by the low selective susceptibility of neoplastic cells interspersed within healthy tissues, which we aim to improve on. Materials & methods: Two superparamagnetic calcium phosphates nanocomposites, that is, iron-doped hydroxyapatite and iron oxide (Mag) nanoparticles coated with amorphous calcium phosphate (Mag@CaP), were synthesized and tested for selective activity against brain and bone cancers. Results: Nanoparticle uptake and intracellular localization were prerequisites for reduction of cancer viability in alternate magnetic fields of extremely low power. Sheer adsorption onto the outer membrane was not sufficient to produce this effect, which was extremely significant for Mag@CaP and iron-doped hydroxyapatite, but negligible for Mag, demonstrating benefits of combining magnetic iron with calcium phosphates. Conclusion: Such selective effects are important in the global effort to rejuvenate clinical prospects of magnetic hyperthermia.

Systematic Study on TiO2 Crystallization via Hydrothermal Synthesis in the Presence of Different Ferrite Nanoparticles as Nucleation Seeds.

In the present work, the crystallization of anatase TiO2 nanoparticles (NPs), using different ferrite nanoparticles with different chemical composition, dimensions and shape as nucleation seeds, was investigated. In particular, CoFe2O4, NiFe2O4 and Fe3O4 NPs with a volume ratio equal to 1:1000 with respect of TiO2 amount, were used in order to investigate the synthesis of nanocrystalline tetragonal anatase TiO2 by a hydrothermal synthesis. In addition, Lu2O3 nanoparticles were also used to detect the effect of a non-magnetic nanoparticle on the synthesis and nanocrystallization of titania. For each sample, a deep physical characterization was performed by XRD (with a Rietveld refinement of the structural data), FE-SEM, STEM, HRTEM, DSC analysis and BET surface area measurement. Furthermore, for some samples, the photocatalytic activity was investigated by degradation of methylene blue in aqueous medium, in the framework of a standard ISO 10678:2010 protocol. The hydrothermal synthesis was performed with a 3 hours' thermal treatment, at a pressure of approximatively 9 bar and a temperature significantly lower (Tmax═150 °C) than the usual temperature necessary to obtain crystalline anatase TiO2 (Tcryst═350 °C). The results give evidence that the mere presence of a nucleation seeds in the hydrothermal reactor, without any particular need for the composition and morphology, leads to crystalline anatase TiO2 nanoparticles with high photocatalytic performances.

Enzymatically promoted release of organic molecules linked to magnetic nanoparticles.

Magnetite-based magnetic nanoparticles have been successfully coupled to an organic system constituted of a fluorescent molecule, a tripeptide specifier and a spacer. The system is able to selectively release the fluorescent molecule upon targeted enzymatic hydrolysis promoted by a lysine/arginine specific protease.

Enhancement of TiO2 NPs Activity by Fe3O4 Nano-Seeds for Removal of Organic Pollutants in Water.

The enhancement of the photocatalytic activity of TiO2 nanoparticles (NPs), synthesized in the presence of a very small amount of magnetite (Fe3O4) nanoparticles, is here presented and discussed. From X-ray diffraction (XRD) and differential scanning calorimetry (DSC) analyses, the crystallinity of TiO2 nanoparticles (NPs) seems to be affected by Fe3O4, acting as nano-seeds to improve the tetragonal TiO2 anatase structure with respect to the amorphous one. Photocatalytic activity data, i.e., the degradation of methylene blue and the Ofloxacin fluoroquinolone emerging pollutant, give evidence that the increased crystalline structure of the NPs, even if correlated to a reduced surface to mass ratio (with respect to commercial TiO2 NPs), enhances the performance of this type of catalyst. The achievement of a relatively well-defined crystal structure at low temperatures (Tmax = 150 °C), preventing the sintering of the TiO2 NPs and, thus, preserving the high density of active sites, seems to be the keystone to understand the obtained results.

Functionalization of Fe3O4 NPs by Silanization: Use of Amine (APTES) and Thiol (MPTMS) Silanes and Their Physical Characterization.

In this paper the results concerning the synthesis of magnetite (Fe3O4) nanoparticles (NPs), their functionalization using silane derivatives, such as (3-Aminopropyl)triethoxysilane (APTES) and (3-mercaptopropyl)trimethoxysilane (MPTMS), and their exhaustive morphological and physical characterization by field emission scanning electron microscopy (FE-SEM) with energy dispersion X-ray spectrometer (EDX) analysis, AC magnetic susceptibility, UV-VIS and IR spectroscopy, and thermogravimetric (TGA) analyses are reported. Two different paths were adopted to achieve the desired functionalization: (1) the direct reaction between the functionalized organo-silane molecule and the surface of the magnetite nanoparticle; and (2) the use of an intermediate silica coating. Finally, the occurrence of both the functionalization with amino and thiol groups has been demonstrated by the reaction with ninhydrin and the capture of Au NPs, respectively.