The responses of immune cells to iron oxide nanoparticles

Abstract

Immune cells play an important role in recognizing and removing foreign objects, such as nanoparticles. Among various parameters, surface coatings of nanoparticles are the first contact with biological system, which critically affect nanoparticle interactions. Here, surface coating effects on nanoparticle cellular uptake, toxicity and ability to trigger immune response were evaluated on a human monocyte cell line using iron oxide nanoparticles. The cells were treated with nanoparticles of three types of coatings (negatively charged polyacrylic acid, positively charged polyethylenimine and neutral polyethylene glycol). The cells were treated at various nanoparticle concentrations (5, 10, 20, 30, 50 μg ml À1 or 2, 4, 8, 12, 20 μg cm À2 ) with 6 h incubation or treated at a nanoparticle concentration of 50 μg ml À1 (20 μg cm À2 ) at different incubation times (6, 12, 24, 48 or 72 h). Cell viability over 80% was observed for all nanoparticle treatment experiments, regardless of surface coatings, nanoparticle concentrations and incubation times. The much lower cell viability for cells treated with free ligands (e.g.~10% for polyethylenimine) suggested that the surface coatings were tightly attached to the nanoparticle surfaces. The immune responses of cells to nanoparticles were evaluated by quantifying the expression of toll-like receptor 2 and tumor necrosis factor-α. The expression of tumor necrosis factor-α and toll-like receptor 2 were not significant in any case of the surface coatings, nanoparticle concentrations and incubation times. These results provide useful information to select nanoparticle surface coatings for biological and biomedical applications.

Effects of engineered nanoparticles on the innate immune system

“…Positively charged NPs enhance the electrostatic attraction between NPs and negatively charged cell membrane, leading to the increased surface endocytosis (or phagocytosis) [56]. Hence, cationic NPs showed higher uptake in macrophage and DCs [57,58]. Hu et al demonstrated that positively charged Fe 2 O 3 NPs enhanced the cross-presentation ability of DCs, while negatively charged Fe 2 O 3 NPs were associated with rapid autophagy [59].…”

Development of an iron quantification method using nuclear magnetic resonance relaxometry

“…15,21,[32][33][34] NMR offers an alternative method for iron quantification when using IONPs as MRI contrast agents, such as r 1 and r 2 relaxivity measurements. Here, an iron quantification method based on NMR relaxometry using a Bruker minispec (mq 60, 60 MHz, 1.4 T) was developed and compared with ICP analysis and ferrozine iron assays.…”

“…Even though the IONPs can be qualitatively visualized by electron microscopy 19 and iron staining, 20 these imaging techniques cannot provide quantitative information of IONPs. The available methods for iron quantification are Inductively coupled plasma mass spectrometry (ICP-MS), 21 atomic absorption spectroscopy (AAS), 22 and ferrozine-based iron assays. 23 ICP analysis is considered the standard method for determining iron concentration with sensitivity down to 100 ppm.…”

Surface functionalization of dopamine coated iron oxide nanoparticles for various surface functionalities

“…cellular uptake [13,38]. DLS measurements (size and zeta potential) were performed at t=0, 30 min, 2 hours, and 4 hours to determine if the NPs experienced non-specific binding of serum proteins on the NPs surfaces.…”

“…Iron oxide nanoparticles (NPs) have been widely studied for biological and biomedical applications, including targeted drug delivery [1], cell tracking [2][3][4][5], and as magnetic resonance imaging(MRI) contrastagents [6][7][8][9].For all these applications, surface functionalities of NPs are critical because they are the first encounter with biological systems. For instance, surfaces directly affect cellular uptake [10], biodistribution [11], blood circulation [12], toxicity [13],and metabolism [14].Many of these biological behaviors can be attributed to the ability of NPs attracting native proteins, also known as protein corona, and subsequently intriguing immune responses [15,16]. Two effective surface coatings have been explored to overcome the surface effects, such asPEGylation [17] and the use ofzwitterionic molecules [18].…”