IEEE TRANSACTIONS ON NANOBIOSCIENCE, VOL. 8, NO. 1, MARCH 2009 33 Magnetically Responsive Nanoparticles for Drug Delivery Applications Using Low Magnetic Field Strengths Shayna L. McGill, Carla L. Cuylear, Natalie L. Adolphi, Marek Osi ´ nski, Senior Member, IEEE, and Hugh D. C. Smyth ∗ Abstract—The purpose of this study is to investigate the poten- tial of magnetic nanoparticles for enhancing drug delivery using a low oscillating magnetic field (OMF) strength. We investigated the ability of magnetic nanoparticles to cause disruption of a viscous biopolymer barrier to drug delivery and the potential to induce triggered release of drug conjugated to the surfaces of these par- ticles. Various magnetic nanoparticles were screened for thermal response under a 295-kHz OMF with an amplitude of 3.1 kA/m. Based on thermal activity of particles screened, we selected the nanoparticles that displayed desired characteristics for evaluation in a simplified model of an extracellular barrier to drug delivery, using lambda DNA/HindIII. Results indicate that nanoparticles could be used to induce DNA breakage to enhance local diffusion of drugs, despite low temperatures of heating. Additional studies showed increased diffusion of quantum dots in this model by single- particle tracking methods. Bimane was conjugated to the surface of magnetic nanoparticles. Fluorescence and transmission electron microscope images of the conjugated nanoparticles indicated little change in the overall appearance of the nanoparticles. A release study showed greater drug release using OMF, while maintaining low bulk heating of the samples (T = 30 ◦ C). This study indicates that lower magnetic field strengths may be successfully utilized for drug delivery applications as a method for drug delivery transport enhancement and drug release switches. Index Terms—Diffusion, DNA, single-particle tracking, super- paramagnetic iron oxide nanoparticles (SPIONs), superparamag- netic nanoparticles, triggered release. Manuscript received November 14, 2008. First published March 16, 2009; current version published June 24, 2009. The work of S. L. McGill was sup- ported by a fellowship from the National Science Foundation (NSF) Integrative Graduate Education and Research Traineeship (IGERT) Program on Integrat- ing Nanotechnology with Cell Biology and Neuroscience (INCBN) under NSF Grant DGE-0549500. Asterisk indicates corresponding author. S. L. McGill and C. L. Cuylear are with the College of Pharmacy, Health Sciences Center, University of New Mexico, Albuquerque, NM 87131 USA (e-mail: smcgill@salud.unm.edu; carlacuy@unm.edu). N. L. Adolphi is with the Department of Biochemistry and Molecular Biology, Health Sciences Center, University of New Mexico, Albuquerque, NM 87131 USA (e-mail: nadolphi@salud.unm.edu). M. Osi´ nski is with the Center of High Technology Materials, Uni- versity of New Mexico, Albuquerque, NM 87106-4343 USA (e-mail: osinski@chtm.unm.edu). ∗ H. D. C. Smyth is with the College of Pharmacy, Health Sciences Cen- ter, University of New Mexico, Albuquerque, NM 87131 USA, and also with Lovelace Respiratory Research Institute, Albuquerque, NM 87108 USA (e-mail: hsmyth@salud.unm.edu). Color versions of one or more of the figures in this paper are available online at http://ieeexplore.ieee.org. Digital Object Identifier 10.1109/TNB.2009.2017292 I. INTRODUCTION S EVERAL recent reviews have outlined the potential for iron oxide magnetic nanoparticles to enhance therapy and drug delivery for biomedical applications [1]–[4]. The primary attractive features of these nanoparticles for applications in biomedicine include their ease of synthesis, ability to be con- trolled remotely via magnetic fields, the intrinsic penetrability of magnetic fields across biological tissues, and their appar- ent biocompatibility. In fact, these attributes have already fa- cilitated their current use as imaging agents during magnetic resonance imaging of the U.S. Food and Drug Administration (FDA) approved products. As a consequence, many researchers are exploring the potential of these magnetic nanoparticles for a variety of applications that can be classified into two func- tionalities: 1) magnetic targeting of drugs associated with the particles [5]–[8] and 2) magnetically induced heating using os- cillating magnetic fields (OMFs) [9]–[11]. In this study, we explore the use of magnetic nanoparticles, commonly referred to as superparamagnetic iron oxide nanoparticles (SPIONs), un- der OMFs to improve diffusive transport of therapeutic agents to enhance drug delivery across biological barriers. We also in- vestigate the potential for achieving triggered release of drug attached to the surfaces of the particles using an OMF. More- over, we explore these opportunities using a lower magnetic field strength than others have previously investigated. Magnetic field hyperthermia has almost solely been applied to cancer therapy where OMFs are used to induce magnetic nanoparticle heating of tissues to about 41 ◦ C–46 ◦ C. Work in this area has been performed for over half a century but a sig- nificant increase in research activity has occurred within the last ten years [12]. Generally, magnetic particles are localized in a target tissue, such as a solid tumor, and an ac magnetic field of sufficient strength and frequency causes the particles to dissipate heat, which is transferred to the tissue and induces hyperthermic apoptosis of cells. In this case, uniform heating of the entire tumor volume (typically several millimeters up to 10 cm in diameter) is desired to destroy malignant tissue, which generally requires field strengths of order 10 kA/m and oscilla- tion frequencies of tens to hundreds of kilohertz [12]. In recent clinical trials in Germany, the field strength was limited to the range 3–14 kA/m (at a frequency of 100 kHz) to limit patient discomfort, which depended on the region treated. Higher fields were tolerated when applied to the head compared to the groin area [13]. 1536-1241/$25.00 © 2009 IEEE