Enhanced Uptake of Fe3O4 Nanoparticles by Intestinal Epithelial Cells in a State of Inflammation

Abstract

Fe3O4 nanoparticles (Fe3O4 NPs) have been used for medical and drug applications, although the mechanisms of cellular uptake and transport need to be further evaluated under inflammatory conditions. In the present study, we investigated the uptake of Fe3O4 NPs (20, 50, 100, and 200 nm) by intestinal epithelial cells under inflammatory conditions via the light scattering of flow cytometry and inductively coupled plasma mass spectrometry (ICP-MS) techniques. The results of the correlation analysis indicated that the uptake ratios of Fe3O4 NPs by intestinal epithelial cells under inflammatory conditions were higher than those under the control conditions. The transportation ratios of NPs by inflammatory Caco-2 cells increased almost 0.8–1.2 fold compared to the control. The internalization of the Fe3O4 NPs in Caco-2 cells was mediated by clathrin-related routes in both the control and an interleukin-1β (IL-1β)-induced inflammatory condition. The level of mRNA of clathrin expressed in Caco-2 cells that were stimulated by IL-1β was almost three times more than the control. Consistently with the mRNA expression, the level of protein in the clathrin was upregulated. Additionally, it was verified for the first time that the expression of clathrin was upregulated in IL-1β-stimulated Caco-2 cells. Collectively, these results provided a further potential understanding about the mechanism of Fe3O4 NPs’ uptake by intestinal epithelial cells under inflammatory conditions.

Optimising PLGA-PEG Nanoparticle Size and Distribution for Enhanced Drug Targeting to the Inflamed Intestinal Barrier

“…Zhou et al, previously reported enhanced uptake of 200 nm Fe 3 O 4 NPs by clathrin-mediated mechanisms in an inflamed caco-2 cell model. Inflamed cells were found to express three times as much clathrin as their healthy counterparts [ 31 ]. It is known in IBD that inflammatory cytokines such as IL-1β, TNF and IFN-γ cause dysregulation of endocytic mechanisms leading to enhanced uptake of tight junction proteins and bacteria which contribute to barrier disruption and disease pathogenesis [ 32 , 33 ].…”

Bacteriophages targeting intestinal epithelial cells: a potential novel form of immunotherapy

“…Furthermore, it has been shown that the uptake and transportation ratios of nanoparticles by IEC in a state of inflammation are enhanced compared with the control [ 41 ]. This phenomenon has clear relevance for the uptake of phages by normal and inflamed IEC.…”

Nano-Nutraceuticals for Health: Principles and Applications

“…The internalization of nanoparticles in cells is influenced by their physicochemical properties and the cells’ microenvironment (Fig. 1 ) (Li and Monteiro-Riviere 2016 ; Brkić Ahmed et al 2017 ; Zhou et al 2017 ; Dreifuss et al 2018 ). The main characteristics involved are size, shape, surface charge, surface functional groups, and hydrophilicity.…”

“…Nanoparticles (NPs) can be uptaken across the plasma membrane by various mechanisms, from passive diffusion to active transport. The endocytic and non-endocytic pathways are the most common among these mechanisms (Kettler et al 2014 ; Zhang et al 2016 ; Brkić Ahmed 2017 ; Zhou et al 2017 ; Dreifuss et al 2018 ). Diffusion is the movement of molecules from more to less concentrated gradients, and usually occurs for small, hydrophobic, and uncharged molecules.…”