Determining iron oxide nanoparticle heating efficiency and elucidating local nanoparticle temperature for application in agarose gel-based tumor model.

Magnetic iron oxide nanoparticles (MNPs) have been developed for magnetic fluid hyperthermia (MFH) cancer therapy, where cancer cells are treated through the heat generated by application of a high frequency magnetic field. This heat has also been proposed as a mechanism to trigger release of chemotherapy agents. In each of these cases, MNPs with optimal heating performance can be used to maximize therapeutic effect while minimizing the required dosage of MNPs. In this study, the heating efficiencies (or specific absorption rate, SAR) of two types of MNPs were evaluated experimentally and then predicted from their magnetic properties. MNPs were also incorporated in the core of poly(ethylene glycol-b-caprolactone) micelles, co-localized with rhodamine B fluorescent dye attached to polycaprolactone to monitor local, nanoscale temperatures during magnetic heating. Despite a relatively high SAR produced by these MNPs, no significant temperature rise beyond that observed in the bulk solution was measured by fluorescence in the core of the magnetic micelles. MNPs were also incorporated into a macro-scale agarose gel system that mimicked a tumor targeted by MNPs and surrounded by healthy tissues. The agarose-based tumor models showed that targeted MNPs can reach hyperthermia temperatures inside a tumor with a sufficient MNP concentration, while causing minimal temperature rise in the healthy tissue surrounding the tumor.

Impact of magnetic field parameters and iron oxide nanoparticle properties on heat generation for use in magnetic hyperthermia.

Heating of nanoparticles (NPs) using an AC magnetic field depends on several factors, and optimization of these parameters can improve the efficiency of heat generation for effective cancer therapy while administering a low NP treatment dose. This study investigated magnetic field strength and frequency, NP size, NP concentration, and solution viscosity as important parameters that impact the heating efficiency of iron oxide NPs with magnetite (Fe3O4) and maghemite (γ-Fe2O3) crystal structures. Heating efficiencies were determined for each experimental setting, with specific absorption rates (SARs) ranging from 3.7 to 325.9 W/g Fe. Magnetic heating was conducted on iron oxide NPs synthesized in our laboratories (with average core sizes of 8, 11, 13, and 18 nm), as well as commercially-available iron oxides (with average core sizes of 8, 9, and 16 nm). The experimental magnetic coil system made it possible to isolate the effect of magnetic field parameters and independently study the effect on heat generation. The highest SAR values were found for the 18 nm synthesized particles and the maghemite nanopowder. Magnetic field strengths were applied in the range of 15.1 to 47.7 kA/m, with field frequencies ranging from 123 to 430 kHz. The best heating was observed for the highest field strengths and frequencies tested, with results following trends predicted by the Rosensweig equation. An increase in solution viscosity led to lower heating rates in nanoparticle solutions, which can have significant implications for the application of magnetic fluid hyperthermia in vivo.

Cocrystals of 10-methylphenthiazine and 1,3-dinitrobenzene: implications for the optical sensing of TNT-based explosives.

The evaporation of an ethanol solution containing an equimolar mixture of 10-methylphenothiazine and 1,3-dinitrobenzene gave red-purple crystals. The diffuse reflection spectrum for the cocrystals showed a low reflectance from the UV through the visible spectrum until the reflectance increased at the red end of the visible spectrum. The crystal structure showed alternating π stacking of the electron-rich 10-methylphenothiazine and the electron-poor 1,3-dinitrobenzene. There were also hydrogen bonding interactions between the nitro groups from 1,3-dinitrobenzene and the aromatic hydrogen atoms from 10-methylphenothiazine. The infrared spectrum showed a shift to lower wavenumbers for the symmetric and antisymmetric stretching modes for the nitro groups. Thin films containing 10-methylphenothiazine in polystyrene were exposed to 1,3-dintrobenzene vapor, and spectroscopic ellipsometry showed an average increase in the refractive index of 0.006 through the entire range of wavelengths from 1000 to 300 nm.

Magnetic Heating of Iron Oxide Nanoparticles and Magnetic Micelles for Cancer Therapy.

The inclusion of magnetic nanoparticles into block copolymer micelles was studied towards the development of a targeted, magnetically triggered drug delivery system for cancer therapy. Herein, we report the synthesis of magnetic nanoparticles and poly(ethylene glycol-b-caprolactone) block copolymers, and experimental verification of magnetic heating of the nanoparticles, self-assembly of the block copolymers to form magnetic micelles, and thermally-enhanced drug release. The semicrystalline core of the micelles melted at temperatures just above physiological conditions, indicating that they could be used to release a chemotherapy agent from a thermo-responsive polymer system. The magnetic nanoparticles were shown to heat effectively in high frequency magnetic fields ranging from 30-70 kA/m. Magnetic micelles also showed heating properties, that when combined with a chemotherapeutic agent and a targeting ligand could be developed for localized, triggered drug delivery. During the magnetic heating experiments, a time lag was observed in the temperature profile for magnetic micelles, likely due to the heat of fusion of melting of polycaprolactone micelle cores before bulk solution temperatures increased. Doxorubicin, incorporated into the micelles, released faster when the micelles were heated above the core melting point.

Polymer micelles with crystalline cores for thermally triggered release.

Interest in the use of poly(ethylene glycol)-b-polycaprolactone diblock copolymers in a targeted, magnetically triggered drug delivery system has led to this study of the phase behavior of the polycaprolactone core. Four different diblock copolymers were prepared by the ring-opening polymerization of caprolactone from the alcohol terminus of poly(ethylene glycol) monomethylether, M(n) ≈ 2000. The critical micelle concentration depended on the degree of polymerization for the polycaprolactone block and was in the range of 2.9 to 41 mg/L. Differential scanning calorimetry curves for polymer solutions with a concentration above the critical micelle concentration showed a melting endotherm in the range of 40 to 45 °C, indicating the polycaprolactone core was semicrystalline. Pyrene was entrapped in the micelle core without interfering with the ability of the polycaprolactone to crystallize. When the polymer solution was heated above the melting point of the micelle core, the pyrene was free to leave the core. Temperature-dependent measurements of the critical micelle concentration and temperature-dependent dynamic light scattering showed that the micelles remain intact at temperatures above the melting point of the polycaprolactone core.

Synthesis and characterization of PtRe alloy nanoparticles as electrocatalysts for methanol oxidation.

We report a new synthesis of PtRe alloy nanoparticles (NPs) and their electrocatalytic activity for methanol oxidation. PtRe alloy NPs with controlled composition were prepared by a capping agents-based colloidal method. In the synthesis, trioctylamine was used as high-boiling solvent, and oleylamine/oleic acid were employed as capping agents to control the particle size and dispersion. The PtRe NPs were fully characterized by TEM, EDX, XRD and XPS. The as-prepared PtRe NPs had a narrow size distribution, and displayed a good dispersion in hydrocarbon solvents. Carbon-supported PtRe catalysts were prepared by physical deposition of as-prepared particles on carbon powder, followed by the catalytic activation at 400 degrees C in Ar/H2. Electrochemical studies showed the PtRe catalysts had high activity for methanol electrooxidation.

Synthesis and Characterization of Multifunctional Chitosan- MnFe2O4 Nanoparticles for Magnetic Hyperthermia and Drug Delivery.

Multifunctional nanoparticles composed of MnFe2O4 were encapsulated in chitosan for investigation of system to combine magnetically-triggered drug delivery and localized hyperthermia for cancer treatment with the previously published capacity of MnFe2O4 to be used as an efficient MRI contrast agent for cancer diagnosis. This paper focuses on the synthesis and characterization of magnetic MnFe2O4 nanoparticles, their dispersion in water and their incorporation in chitosan, which serves as a drug carrier. The surface of the MnFe2O4 nanoparticles was modified with meso-2,3-di-mercaptosuccinic acid (DMSA) to develop stable aqueous dispersions. The nanoparticles were coated with chitosan, and the magnetic properties, heat generation and hydrodynamic size of chitosan-coated MnFe2O4 were evaluated for various linker concentrations and in a range of pH conditions.

Synthesis and magnetic properties of FePt nanoparticles with hard nonmagnetic shells.

Chemically synthesized FePt nanoparticles were coated with nonmagnetic SiO2 and MnO shells by sol-gel and polyol processes. TEM images show that the FePt/SiO2 nanoparticles exhibit a thick spherical shell. The size and morphology of the MnO shell can be controlled by changing the reaction temperature, the molar ratio of surfactants/Mn(acac)2, and/or the concentration of precursor. The morphology of the MnO shell can be either spherical-like or cubic-like, depending on whether the molar ratio of surfactants/Mn(acac)2 is less than or larger than 2. From XRD measurements, the spherical core/shell nanoparticles exhibit 3D random crystallographic orientation, while the cubic core/shell nanoparticles prefer (200) texture. The magnetic moment of FePt particles can be enhanced by coating with SiO2 and MnO shells. Furthermore, the agglomeration of FePt particles upon the thermal annealing can be significantly inhibited with SiO2 and MnO shells.

Effect of sintered grain growth on chemical ordering in binary FePt/Cu nanoparticle arrays.

Recent studies have shown a strong correlation between grain growth and chemical ordering in chemically synthesized FePt nanoparticles. In order to study this effect, we have prepared a series of samples in which 3.5 nm FePt nanoparticles are dispersed in a matrix of Cu nanoparticles. The samples were annealed at 600 degrees C and at 800 degrees C. Grain size was determined by XRD Scherrer analysis and time-dependent remanent coercivity measurements were made to determine the intrinsic remanent coercivity, Hcr0. For samples annealed at 600 degrees C, Hcr0 increases strongly with grain size up to approximately 5 nm and increases weakly with additional grain growth. By contrast, after annealing at 800 degrees C, Hcr0 appears nearly independent of grain size. The results suggest that isolated 3.5 nm FePt nanoparticles can be weakly ordered when annealed at 600 degrees C and sintering is necessary for significant chemical ordering.

Understanding mercapto ligand exchange on the surface of FePt nanoparticles.

Tailoring the surface of nanoparticles is essential for biological applications of magnetic nanoparticles. FePt nanoparticles are interesting candidates owing to their high magnetic moment. Established procedures to make FePt nanoparticles use oleic acid and oleylamine as the surfactants, which make them dispersed in nonpolar solvents such as hexane. As a model study to demonstrate the modification of the surface chemistry, stable aqueous dispersions of FePt nanoparticles were synthesized after ligand exchange with mercaptoalkanoic acids. This report focuses on understanding the surface chemistry of FePt upon ligand exchange with mercapto compounds by conducting X-ray photoelectron spectroscopy (XPS) and Fourier transform infrared spectroscopy (FTIR) studies. It was found that the mercapto end displaces oleylamine on the Pt atoms and the carboxylic acid end displaces the oleic acid on the Fe atoms, thus exposing carboxylate and thiolate groups on the surface that provide the necessary electrostatic repulsion to form stable aqueous dispersions of FePt nanoparticles.

Covalently linked Au nanoparticles to a viral vector: potential for combined photothermal and gene cancer therapy.

Hyperthermia can be produced by near-infrared laser irradiation of gold nanoparticles present in tumors and thus induce tumor cell killing via a bystander effect. To be clinically relevant, however, several problems still need to be resolved. In particular, selective delivery and physical targeting of gold nanoparticles to tumor cells are necessary to improve therapeutic selectivity. Considerable progress has been made with respect to retargeting adenoviral vectors for cancer gene therapy. We therefore hypothesized that covalent coupling of gold nanoparticles to retargeted adenoviral vectors would allow selective delivery of the nanoparticles to tumor cells, thus feasibilizing hyperthermia and gene therapy as a combinatorial therapeutic approach. For this, sulfo-N-hydroxysuccinimide labeled gold nanoparticles were reacted to adenoviral vectors encoding a luciferase reporter gene driven by the cytomegalovirus promoter (AdCMVLuc). We herein demonstrate that covalent coupling could be achieved, while retaining virus infectivity and ability to retarget tumor-associated antigens. These results indicate the possibility of using adenoviral vectors as carriers for gold nanoparticles.

Enhanced magnetic properties of self-assembled FePt nanoparticles with MnO shell.

Self-assembled FePt/MnO nanoparticles with different morphology and size were synthesized with a polyol process. With the MnO coating, FePt nanoparticles exhibit a high blocking temperature and magnetic moment. The low-temperature hysteresis loop of FePt nanoparticles can be shifted through the AFM pinning of the MnO shell. The aggregation of FePt nanoparticles during the L10 phase transformation can be significantly decreased by coating with the MnO shell.

Combination of viral biology and nanotechnology: new applications in nanomedicine.

Viruses are well known for their ability to cause disease, but their beneficial usefulness as vectors for gene therapy have been noted as well. As an extension of their use in a gene therapy context, their combination with nanotechnology is starting to benefit many areas of science and medicine. These include nanofabrication and medical diagnostics, to name a few, as well as viro-nanotherapy, here defined as the combination of viral biology with nanotechnology to create new therapeutic avenues to treat disease. This review provides examples of areas wherein viruses in combination with nanotechnology are being used to either advance scientific knowledge or accelerate the development of new diagnostics and therapeutics for human pathological conditions.