Abstract 4661: Magnetic nanoparticles (MNPs) for cancer drug delivery: The value of in vitro modeling

Abstract

Abstract BACKGROUND: Magnetic nanoparticles (MNPs) have attracted great interest for use as delivery vehicles for cancer and other diseases due to their ability to be functionalized and localized using external magnets. In the presence of a magnetic field, individual MNPs form aggregates, which in turn can be made to spin and surface walk, in response to rotation of the field. Here, we present data from the use of a in vitro model system, which is useful in mimicking the various conditions and distances that MNP-drug combinations may encounter in vivo. METHODS: A sterilizable acrylic tray was designed, which has 1/8th inch wide lanes and can be used with or without the addition of cultured cells. The tray is compatible with standard plate readers, and the lanes can be modified to mimic various conduits within the body. In studies described here, glioma cell lines and normal vascular endothelial cells were used in the tray. In order to test the effect of fluid viscosity on MNP velocity in response to the rotating magnetic field, lanes were filled with 1mL of PBS, culture medium, serum, or whole blood. Pre-magnetized and unmagnetized MNPs were aliquoted into the lanes at volumes from 10 - 100 uL. T-PA and trypan blue were used as a model drugs. Velocities of MNP aggregates were determined by videography at five different tray positions relative to the magnet: centered, offset, push, pull, and below. Particle adhesion to cells could be quantified using ImageJ. RESULTS: Using the model system, greater MNP velocities were achieved with pre-magnetization, and larger aliquots. For example, 100ul aliquots had a total average velocity 1.27± 0.21 times that of 20ul. MNP velocity was found to be inversely -related to fluid viscosity, but particles could be moved magnetically even through whole blood. Test drugs could be successfully delivered by convection, even without prior binding to MNPs. MNP velocity also varied according to magnet position, with speeds up to 0.75 +/- 0.05 cm/sec in the pull (fastest) position. In the offset position, a distance of 20 cm above the magnet produced the greatest velocity. MNPs moved more slowly over confluent monolayers of endothelial or glioma cells (with greater adhesion), but a mean velocity of 0.25 cm/sec +/- 0.03 cm was typically observed. CONCLUSIONS: In vitro modeling is extremely helpful in predicting the behavior of particles intended for clinical use in magnetically-enhanced drug delivery. The velocity and cell surface adhesion of MNP aggregates can be quantified, and the effect of factors - such as fluid viscosity, cell type, and position with respect to the magnet - analyzed in order to better understand the advantages and limitations of this technology. Citation Format: Sebastian P. Pernal, Alexander J. Willis, Herbert H. Engelhard. Magnetic nanoparticles (MNPs) for cancer drug delivery: The value of in vitro modeling [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2018; 2018 Apr 14-18; Chicago, IL. Philadelphia (PA): AACR; Cancer Res 2018;78(13 Suppl):Abstract nr 4661.