Biocompatible, Superparamagnetic, Flame Synthesized Iron Oxide Nanoparticles: Cellular Uptake and Toxicity Studies

Abstract

Superparamagnetic iron oxide nanoparticles, including magnetite (Fe3O4), are widely used in applications such as targeted drug delivery, magnetic resonance imaging, tissue engineering, gene therapy, hyperthermic malignant cell treatment, and cell membrane manipulation. These nanoparticles are particularly interesting for in vivo and in vitro applications since they do not exhibit magnetic behavior once the magnetic field has been removed. In the current work, superparamagnetic iron oxide nanoparticles were produced using a flame synthesis method, which provides significant advantages over other material synthesis processes such as solgel processing, chemical vapor deposition, and laser ablation. Flame synthesis allows control of particle size, size distribution, phase and composition by altering flame operating conditions. Flame synthesis is further capable of commercial production rates with minimal post-processing of the final product materials. This study focuses on the interaction of flame synthesized iron oxide nanoparticles with porcine aortic endothelial cells and compares the results to those obtained using commercially available iron oxide nanoparticles. The materials characteristics of the flame synthesized iron oxide nanoparticles, including morphology, elemental composition, particle size, were analyzed by electron microscopy (TEM, ESEM, EDS), and Raman Spectroscopy. The data verified production of a heterogenous mixture of hematite and magnetite nanoparticles, which exhibit superparamagnetic properties. Monodisperse iron oxide particles of 6–12 nm diameter and aggregated clusters of these 6–12nm nanoparticles have been synthesized. Nanoparticle biocompatibility was assessed by incubating flame synthesized and commercially available iron oxide nanoparticles with endothelial cells for 24 hours. Both alamar blue and Live/Dead cell assays showed no significant toxicity difference between flame synthesized and commercially available nanoparticles. Cells exposed to both types of nanoparticles maintained membrane integrity, as indicated by minimal lactase dehydrogenase release. Endothelial cells imaged by ESEM and confirmed by EDS demonstrated that uncoated flame synthesized nanoparticles are ingested into cells in a similar manner to commercially available nanoparticles. These data suggest that flame synthesized iron oxide nanoparticles are comparable to commercially available nanoparticles for biological applications. Flame synthesis has the advantage of a relatively simple synthesis process with higher purity products and lower time and energy manufacturing costs. Future work will include functionalizing the nanoparticle surfaces for specific biological applications, including specific cell targeting and bioactive factor delivery.