Functionalized Magnetic Force Enhances Magnetic Nanoparticle Guidance: From Simulation to Crossing of the Blood-Brain Barrier in Vivo

In recent studies, we introduced the concept of functionalized magnetic force as a method to prevent nanoparticles from sticking to vessel walls caused by extensive simulation and in vitro experiments involving a Y-shaped channel. In this paper, we further investigated the effectiveness of the functionalized magnetic force with a realistic 3-D vessel through simulations. For the simulations, we considered a more realistic continuous injection of particles with different magnetic forces and frequencies. Based on the results from our simulation studies, we performed in vivo mice experiments to evaluate the effectiveness of using a functionalized magnetic force to aid magnetic nanoparticles (MNPs) in crossing the blood-brain barrier (BBB). To implement the functionalized magnetic force, we developed an electromagnetic actuator regulated by a programmable direct current power supply. Our results indicate that a functionalized magnetic field (FMF) can effectively prevent MNPs from sticking, and also guide them across the BBB. We used 770 nm fluorescent carboxyl MNPs in this paper. Following intravenous administration of MNPs into mice, we applied an external magnetic field to mediate transport of the MNPs across the BBB and into the brain. Furthermore, we evaluated the differential effects of FMFs (0.25, 0.5, and 1 Hz) and constant magnetic fields (CMFs) on the transport of MNPs across the BBB. Our results showed that an FMF is more effective than a CMF in the transport and uptake of MNPs across the BBB in mice. In particular, applying an FMF with a 3 A current and 0.5 Hz frequency mediated the greatest transport and uptake of MNPs across the BBB in mice.