Tarun Vemulkar

Rotating magnetic field induced oscillation of magnetic particles for in vivo mechanical destruction of malignant glioma.

Magnetic particles that can be precisely controlled under a magnetic field and transduce energy from the applied field open the way for innovative cancer treatment. Although these particles represent an area of active development for drug delivery and magnetic hyperthermia, the in vivo anti-tumor effect under a low-frequency magnetic field using magnetic particles has not yet been demonstrated. To-date, induced cancer cell death via the oscillation of nanoparticles under a low-frequency magnetic field has only been observed in vitro. In this report, we demonstrate the successful use of spin-vortex, disk-shaped permalloy magnetic particles in a low-frequency, rotating magnetic field for the in vitro and in vivo destruction of glioma cells. The internalized nanomagnets align themselves to the plane of the rotating magnetic field, creating a strong mechanical force which damages the cancer cell structure inducing programmed cell death. In vivo, the magnetic field treatment successfully reduces brain tumor size and increases the survival rate of mice bearing intracranial glioma xenografts, without adverse side effects. This study demonstrates a novel approach of controlling magnetic particles for treating malignant glioma that should be applicable to treat a wide range of cancers.

Controlled Payload Release by Magnetic Field Triggered Neural Stem Cell Destruction for Malignant Glioma Treatment

Stem cells have recently garnered attention as drug and particle carriers to sites of tumors, due to their natural ability to track to the site of interest. Specifically, neural stem cells (NSCs) have demonstrated to be a promising candidate for delivering therapeutics to malignant glioma, a primary brain tumor that is not curable by current treatments, and inevitably fatal. In this article, we demonstrate that NSCs are able to internalize 2 μm magnetic discs (SD), without affecting the health of the cells. The SD can then be remotely triggered in an applied 1 T rotating magnetic field to deliver a payload. Furthermore, we use this NSC-SD delivery system to deliver the SD themselves as a therapeutic agent to mechanically destroy glioma cells. NSCs were incubated with the SD overnight before treatment with a 1T rotating magnetic field to trigger the SD release. The potential timed release effects of the magnetic particles were tested with migration assays, confocal microscopy and immunohistochemistry for apoptosis. After the magnetic field triggered SD release, glioma cells were added and allowed to internalize the particles. Once internalized, another dose of the magnetic field treatment was administered to trigger mechanically induced apoptotic cell death of the glioma cells by the rotating SD. We are able to determine that NSC-SD and magnetic field treatment can achieve over 50% glioma cell death when loaded at 50 SD/cell, making this a promising therapeutic for the treatment of glioma.

Highly tunable perpendicularly magnetized synthetic antiferromagnets for biotechnology applications

Magnetic micro and nanoparticles are increasingly used in biotechnological applications due to the ability to control their behavior through an externally applied field. We demonstrate the fabrication of particles made from ultrathin perpendicularly magnetized CoFeB/Pt layers with antiferromagnetic interlayer coupling. The particles are characterized by zero moment at remanence, low susceptibility at low fields, and a large saturated moment created by the stacking of the basic coupled bilayer motif. We demonstrate the transfer of magnetic properties from thin films to lithographically defined 2 μm particles which have been lifted off into solution. We simulate the minimum energy state of a synthetic antiferromagnetic bilayer system that is free to rotate in an applied field and show that the low field susceptibility of the system is equal to the magnetic hard axis followed by a sharp switch to full magnetization as the field is increased. This agrees with the experimental results and explains the behaviour of the particles in solution.

Magnetic particles with perpendicular anisotropy for mechanical cancer cell destruction

We demonstrate the effectiveness of out-of-plane magnetized magnetic microdiscs for cancer treatment through mechanical cell disruption under an applied rotating magnetic field. The magnetic particles are synthetic antiferromagnets formed from a repeated motif of ultrathin CoFeB/Pt layers. In-vitro studies on glioma cells are used to compare the efficiency of the CoFeB/Pt microdiscs with Py vortex microdiscs. It is found that the CoFeB/Pt microdiscs are able to damage 62 ± 3% of cancer cells compared with 12 ± 2% after applying a 10 kOe rotating field for one minute. The torques applied by each type of particle are measured and are shown to match values predicted by a simple Stoner-Wohlfarth anisotropy model, giving maximum values of 20 fNm for the CoFeB/Pt and 75 fNm for the Py vortex particles. The symmetry of the anisotropy is argued to be more important than the magnitude of the torque in causing effective cell destruction in these experiments. This work shows how future magnetic particles can be successfully designed for applications requiring control of applied torques.

The mechanical response in a fluid of synthetic antiferromagnetic and ferrimagnetic microdiscs with perpendicular magnetic anisotropy

In this article, we demonstrate the magneto-mechanic behavior in a fluid environment of perpendicularly magnetized microdiscs with antiferromagnetic interlayer coupling. When suspended in a fluid and under the influence of a simple uniaxial applied magnetic field sequence, the microdiscs mechanically rotate to access the magnetic saturation processes that are either that of the easy axis, hard axis, or in-between the two, in order to lower their energy. Further, these transitions enable the magnetic particles to form reconfigurable magnetic chains, and transduce torque from uniaxial applied fields. These microdiscs offer an attractive platform for the fabrication of fluid based micro- and nanodevices, and dynamically self assembled complex architectures.

The effect of underlayers on the reversal of perpendicularly magnetized multilayer thin films for magnetic micro- and nanoparticles

Perpendicularly magnetized microparticles offer the ability to locally apply high torques on soft matter under an applied magnetic field. These particles are engineered to have a zero remanence magnetic configuration via synthetic antiferromagnetic coupling using a Ru coupling interlayer. The flexibility offered by the top down thin film fabrication process in a CoFeB/Pt perpendicular thin film is demonstrated by using the Pt interlayer thicknesses in a Pt/Ru/Pt antiferromagnetic coupling multilayer to tune the applied magnetic field value of the easy axis spin-flip transition to saturation and hence the field value at which the magnetic particles are magnetically activated via a distinct transition to saturation. The importance of a Ta buffer layer on the magnetic behavior of the stack is shown. While Au capping layers are desirable for biotechnology applications, we demonstrate that they can drastically change the nucleation and propagation of domains in the film, thereby altering the reversal behavior ...

Research data supporting "The mechanical response in a fluid of synthetic antiferromagnetic and ferrimagnetic microdiscs with perpendicular magnetic anisotropy"

This dataset is the magnetometry data for the publication listed above with Applied Physics Letters.