Magnetic Nanoparticles for Combination Cancer Therapy: Synthesis and Characterization of Flow Behavior in Simulated Blood Vessels

Lauren M. Blue, Mary Kathryn Sewell, Dong-Hyun Kim, and Christopher S. Brazel. Chemical and Biological Engineering, University of Alabama, Tuscaloosa, AL 35487

INTRODUCTION: Localization of anti-cancer agents is key in increasing treatment efficacy and decreasing negative patient side effects. Magnetic nanoparticles can be used to locally target therapies while also offering a combination of hyperthermia treatment when exposed to an AC field and triggered release of anti-cancer agents. In this study, localization of magnetic nanoparticles by application of a static magnetic field was investigated to determine nanoparticle retention in a simulated blood vessel. METHODS: Magnetic cobalt ferrite nanoparticles were synthesized, dispersed in aqueous solution and labeled with a rhodamine tag to visualize flow patterns in a flow cell, as monitored by a fluorescence microscope. Nanoparticles were characterized for particle size and magnetic susceptibility. The flow behavior was analyzed with respect to magnetic field strength, flow velocity, and nanoparticle concentration. Nanoparticle retention was analyzed by UV-Visible spectrophotometry. Chitosan, a pH-responsive polymer, was coated on the nanoparticle surface through a linking reaction. These coated particles were characterized for structure and magnetization. Also, drug loading efficiencies of the model drug Theophylline was determined. RESULTS: Cobalt ferrite nanoparticles were synthesized in the size range of 7 to 10 nm, and were shown to heat effectively using an AC magnetic field of 380 to 634 Gauss in the frequency 266 kHz. The gradient of fluorescent intensity in the flow cell for rhodamine labeled particles could be used to monitor changes to flow patterns caused by magnetic fields placed outside the simulated blood vessel. TEM determined that Chitosan was grafted to the nanoparticle surface, and UV-visible spectrophotometry determined drug loading efficiency with respect to Chitosan thickness. CONCLUSION: The novel materials investigated here show promise for the development of a multifunctional nano-scale device that can be targeted magnetically and triggered to deliver medication from a thermoresponsive coating in addition to localized hyperthermia by means of an AC magnetic field.