Quantitative magnetic force microscopy using calibration on superconducting flux quanta.

We present a new procedure that takes advantage of the magnetic flux quantization of superconducting vortices to calibrate the magnetic properties of tips for magnetic force microscopy (MFM). Indeed, a superconducting vortex, whose quantized flux is dependent upon Plank constant, speed of light and electron charge, behaves as a very well defined magnetic reference object. The proposed calibration procedure has been tested on new and worn tips and shows that the monopole point-like approximation of the probe is a reliable model. This procedure has been then applied to perform quantitative MFM experiments on a soft ferromagnetic thin film of permalloy, leading to the determination of the local out-of-plane component of the canted magnetization, together with its spatial variations across a few µm2 scan area.

Nontrivial Nature and Penetration Depth of Topological Surface States in SmB_{6} Thin Films.

The nontrivial feature and penetration depth of the topological surface states (TSS) in SmB_{6} were studied via spin pumping. The experiments used SmB_{6} thin films grown on the bulk magnetic insulator Y_{3}Fe_{5}O_{12} (YIG). Upon the excitation of magnetization precession in the YIG, a spin current is generated in the SmB_{6} that produces, via spin-orbit coupling, a lateral electrical voltage in the film. This spin-pumping voltage signal becomes considerably stronger as the temperature decreases from 150 to 10 K, and such an enhancement most likely originates from the spin-momentum locking of the TSS and may thereby serve as evidence for the nontrivial nature of the TSS. The voltage data also show a unique film thickness dependence that suggests a TSS depth of ∼32 nm. The spin-pumping results are supported by transport measurements and analyses using a tight binding model.

The effect of ligands on FePt-Fe3O4 core-shell magnetic nanoparticles.

FePt-Fe3O4 core-shell nanoparticles functionalized with 3,4-dihydroxyphenylacetic acid (DOPAC) and dimercaptosuccinic acid (DMSA) ligands were synthesized and characterized. We found that the DOPAC ligand enhances the magnetic properties of the FePt-Fe3O4 particles, in comparison with the DMSA ligand, which induces the oxidation of the shell layer that causes a significant reduction of the saturation magnetization. The synthesized magnetic nanoparticles were evaluated for applications in magnetic hyperthermia and magnetic resonance imaging contrast enhancement.

Stimuli-responsive magnetic nanomicelles as multifunctional heat and cargo delivery vehicles.

Hybrid nanoarchitectures are among the most promising nanotechnology-enabled materials for biomedical applications. Interfacing of nanoparticles with active materials gives rise to the structures with unique multiple functionality. Superparamagnetic iron oxide nanoparticles particles SPION are widely employed in the biology and in developing of advanced medical technologies. Polymeric micelles offer the advantage of multifunctional carriers which can serve as delivery vehicles carrying nanoparticles, hydrophobic chemotherapeutics and other functional materials and molecules. Stimuli-responsive polymers are especially attractive since their properties can be modulated in a controlled manner. Here we report on multifunctional thermo-responsive poly(N-isopropylacrylamide-co-acrylamide)-block-poly(ε-caprolactone) random block copolymer micelles as magnetic hyperthermia-mediated payload release and imaging agents. The combination of copolymers, nanoparticles and doxorubicin drug was tailored the way that the loaded micelles were cable to respond to magnetic heating at physiologically-relevant temperatures. A surface functionalization of the micelles with the integrin ß4 antibody and consequent interfacing of the resulting nanobio hybrid with squamous head and neck carcinoma cells which is known to specifically over-express the A9 antigen resulted in concentration of the micelles on the surface of cells. No inherent cytotoxicity was detected for the magnetic micelles without external stimuli application. Furthermore, SPION-loaded micelles demonstrate significant MRI contrast enhancement abilities.

Multifunctional ferromagnetic disks for modulating cell function.

In this work, we focus on the methods for controlling cell function with ferromagnetic disk-shaped particles. We will first review the history of magnetically assisted modulation of cell behavior and applications of magnetic particles for studying physical properties of a cell. Then, we consider the biological applications of the microdisks such as the method for induction of cancer cell apoptosis, controlled drug release, hyperthermia and MRI imaging.

Biofunctionalized magnetic-vortex microdiscs for targeted cancer-cell destruction.

Nanomagnetic materials offer exciting avenues for probing cell mechanics and activating mechanosensitive ion channels, as well as for advancing cancer therapies. Most experimental works so far have used superparamagnetic materials. This report describes a first approach based on interfacing cells with lithographically defined microdiscs that possess a spin-vortex ground state. When an alternating magnetic field is applied the microdisc vortices shift, creating an oscillation, which transmits a mechanical force to the cell. Because reduced sensitivity of cancer cells toward apoptosis leads to inappropriate cell survival and malignant progression, selective induction of apoptosis is of great importance for the anticancer therapeutic strategies. We show that the spin-vortex-mediated stimulus creates two dramatic effects: compromised integrity of the cellular membrane, and initiation of programmed cell death. A low-frequency field of a few tens of hertz applied for only ten minutes was sufficient to achieve approximately 90% cancer-cell destruction in vitro.

Gold Nanoparticles-enabled Efficient Dual Delivery of Anticancer Therapeutics to HeLa Cells.

Colloidal gold nanoparticles (AuNPs) are of interest as non-toxic carriers for drug delivery owing to their advanced properties, such as extensive surface-to-volume ratio and possibilities for tailoring their charge, hydrophilicity and functionality through surface chemistries. To date, various biocompatible polymers have been used for surface decoration of AuNPs to enhance their stability, payloads capacity and cellular uptake. This study describes a facile one-step method to synthesize stable AuNPs loaded with combination of two anticancer therapeutics, -bleomycin and doxorubicin. Anticancer activities, cytotoxicity, uptake and intracellular localization of the AuNPs were demonstrated in HeLa cells. We show that the therapeutic efficacy of the nanohybrid drug was strongly enhanced by the active targeting by the nanoscale delivery system to HeLa cells with a significant decrease of the half-maximal effective drug concentration, through blockage of HeLa cancer cell cycle. These results provide rationale for further progress of AuNPs-assisted combination chemotherapy using two drugs at optimized effective concentrations which act via different mechanisms thus decreasing possibilities of development of the cancer drug resistance, reduction of systemic drug toxicity and improvement of outcomes of chemotherapy.

Cell-Free Synthetic Biology Chassis for Nanocatalytic Photon-to-Hydrogen Conversion.

We report on an entirely man-made nano-bio architecture fabricated through noncovalent assembly of a cell-free expressed transmembrane proton pump and TiO2 semiconductor nanoparticles as an efficient nanophotocatalyst for H2 evolution. The system produces hydrogen at a turnover of about 240 µmol of H2 (µmol protein)-1 h-1 and 17.74 mmol of H2 (µmol protein)-1 h-1 under monochromatic green and white light, respectively, at ambient conditions, in water at neutral pH and room temperature, with methanol as a sacrificial electron donor. Robustness and flexibility of this approach allow for systemic manipulation at the nanoparticle-bio interface toward directed evolution of energy transformation materials and artificial systems.

Study of functional infrared imaging for early detection of mucositis in locally advanced head and neck cancer treated with chemoradiotherapy.

BACKGROUND AND PURPOSE: Chemoradiotherapy (CRT) has led to improved efficacy in treating locally advanced squamous cell carcinoma of the head and neck (LA-SCCHN) but has led to almost universal in-field mucositis. Patients treated with the same regimen often have differences in mucositis occurrence and severity. Mucositis induced via radiation is known to represent an intense inflammatory response histologically. We hypothesized that patients destined to display severe mucocutaneous toxicity would demonstrate greater alterations in thermal intensity early in therapy than identically treated counterparts. This will allow identification of patients that will require more intensive supportive care using thermal imaging technology. MATERIALS AND METHODS: Subjects with LA-SCCHN (oral cavity or oropharynx) being treated with the identical chemoradiotherapy regimen underwent baseline and weekly thermal imaging. Changes in skin temperature caused by mucositis and dermatitis compared with a reference area (ΔT were calculated and correlated to grade of mucositis based on NCI-CTCAE 3.0. RESULTS: Thirty-four subjects were enrolled. Grade 3 mucositis and dermatitis was observed in 53% and 21%, respectively. We observed a statistically significant positive association between an early rise in ΔT and mucositis grade (p value=0.03). CONCLUSIONS: Thermal imaging is able to detect small and early changes in skin surface temperature that may be associated with development of mucositis in patients being treated with chemoradiotherapy.

Microfabricated magnetic structures for future medicine: from sensors to cell actuators.

In this review, we discuss the prospective medical application of magnetic carriers microfabricated by top-down techniques. Physical methods allow the fabrication of a variety of magnetic structures with tightly controlled magnetic properties and geometry, which makes them very attractive for a cost-efficient mass-production in the fast growing field of nanomedicine. Stand-alone fabricated particles along with integrated devices combining lithographically defined magnetic structures and synthesized magnetic tags will be considered. Applications of microfabricated multifunctional magnetic structures for future medicinal purposes range from ultrasensitive in vitro diagnostic bioassays, DNA sequencing and microfluidic cell sorting to magnetomechanical actuation, cargo delivery, contrast enhancement and heating therapy.

Nano-structured magnetic metamaterial with enhanced nonlinear properties.

Nano-structuring can significantly modify the properties of materials. We demonstrate that size-dependent modification of the spin-wave spectra in magnetic nano-particles can affect not only linear, but also nonlinear magnetic response. The discretization of the spectrum removes the frequency degeneracy between the main excitation mode of a nano-particle and the higher spin-wave modes, having the lowest magnetic damping, and reduces the strength of multi-magnon relaxation processes. This reduction of magnon-magnon relaxation for the main excitation mode leads to a dramatic increase of its lifetime and amplitude, resulting in the intensification of all the nonlinear processes involving this mode. We demonstrate this experimentally on a two-dimensional array of permalloy nano-dots for the example of parametric generation of a sub-harmonic of an external microwave signal. The characteristic lifetime of this sub-harmonic is increased by two orders of magnitude compared to the case of a continuous magnetic film, where magnon-magnon relaxation limits the lifetime.

A novel adenoviral vector labeled with superparamagnetic iron oxide nanoparticles for real-time tracking of viral delivery.

In vivo tracking of gene therapy vectors challenges the investigation and improvement of biodistribution of these agents in the brain, a key feature for their targeting of infiltrative malignant gliomas. The glioma-targeting Ad5/3-cRGD gene therapy vector was covalently bound to super-paramagnetic iron oxide (Fe(3)O(4)) nanoparticles (SPION) to monitor its distribution by MRI. Transduction of labeled and unlabeled vectors was assessed on the U87 glioma cell line and normal human astrocytes (NHA), and was higher in U87 compared to NHA, but was similar between labeled and unlabeled virus. An in vivo study was performed by intracranial subcortical injection of labeled-Ad5/3-cRGD particles into a pig brain. The labeled vector appeared in vivo as a T2-weighted hyperintensity and a T2-gradient echo signal at the injection site, persisting up to 72 hours post-injection. We describe a glioma-targeting vector that is labeled with SPION, thereby allowing for MRI detection with no change in transduction capability.