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

• Published in: Journal of controlled release Vol. 223; pp. 75 - 84
• Main Authors: Cheng, Yu, Muroski, Megan E., Petit, Dorothée C.M.C., Mansell, Rhodri, Vemulkar, Tarun, Morshed, Ramin A., Han, Yu, Balyasnikova, Irina V., Horbinski, Craig M., Huang, Xinlei, Zhang, Lingjiao, Cowburn, Russell P., Lesniak, Maciej S.
• Format: Journal Article
• Language: English
• Published: Netherlands Elsevier B.V 10.02.2016
• Subjects: adverse effects; Animals; antineoplastic activity; Apoptosis; Brain - metabolism; Brain - pathology; brain neoplasms; Brain Neoplasms - drug therapy; Brain Neoplasms - metabolism; Brain Neoplasms - pathology; Cell Line, Tumor; cell structures; drugs; energy; fever; Glioma - drug therapy; Glioma - metabolism; Glioma - pathology; Humans; Magnetic field; Magnetic Fields; Magnetic particles; Male; Malignant glioma; Mechanical destruction; Mice; Mice, Nude; Microscopy, Electron, Transmission; nanoparticles; Nanoparticles - administration & dosage; Nanoparticles - therapeutic use; survival rate; Tissue Distribution; Tumor Burden; Malignant glioma; Magnetic particles; Mechanical destruction; Magnetic field
• ISSN: 0168-3659; 1873-4995; 1873-4995
• DOI: 10.1016/j.jconrel.2015.12.028

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. [Display omitted]