(326d) Award Submission: Surface-Dependent Biological Response of Human Monocytes to Iron Oxide Nanoparticles

Iron oxide nanoparticles (NPs) have been widely explored for targeted drug delivery, localized therapy, and as contrast agents for magnetic resonance imaging (MRI).  For all these applications, iron oxide NPs need to be injected into the human body and directly interact with the patient immune system.  Therefore, it is of great importance to study the immune response of monocyte cells to iron oxide NPs.  Monocytes are essential in the body’s primary response to pathogens, which make them an ideal candidate for immune response studies.  In this study, the monocytes were treated with varying concentrations of polyacrylic acid (PAA)-, polyethylenimine (PEI)-, and polysorbate 80- coated iron oxide NPs.  Concentration and time-dependent cytotoxicity and immune responses were conducted.

The 3-(4,5-Dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) assay confirmed that our iron oxide NPs can be practically used for biomedical applications due to the observed high cell viability (> 80%) for all the samples. Surprisingly, the cytotoxicity tests showed little dependence on the surface functionality based on the cell death trends from different types of NPs. The specific NP-cell interaction mechanisms will be investigated in the future. The effective internalization of the iron oxide NPs by the monocytes were clearly observed under transmission electron microscopy (TEM). Further, the cellular uptake efficiency of NPs as a function of surface chemistries was quantified using inductively coupled plasma-emission spectrometer (ICP). The immune response was primarily analyzed by monitoring the immune biomarkers: tumor necrosis factor (TNF)-α and toll-like receptors 2 (TLR-2). These studies will provide valuable information on the understanding of the surface-dependent cytotoxicity, cellular uptake, and immune response.

This work is funded by NFS-DMR 0907204 and EEC-1005191.