Epidermal Growth Factor Enhances Cellular Uptake of Polystyrene Nanoparticles by Clathrin-Mediated Endocytosis.

Le Phuc,Akiyoshi Taniguchi

doi:10.3390/ijms18061301

Abstract

The interaction between nanoparticles and cells has been studied extensively, but most research has focused on the effect of various nanoparticle characteristics, such as size, morphology, and surface charge, on the cellular uptake of nanoparticles. In contrast, there have been very few studies to assess the influence of cellular factors, such as growth factor responses, on the cellular uptake efficiency of nanoparticles. The aim of this study was to clarify the effects of epidermal growth factor (EGF) on the uptake efficiency of polystyrene nanoparticles (PS NPs) by A431 cells, a human carcinoma epithelial cell line. The results showed that EGF enhanced the uptake efficiency of A431 cells for PS NPs. In addition, inhibition and localization studies of PS NPs and EGF receptors (EGFRs) indicated that cellular uptake of PS NPs is related to the binding of EGF–EGFR complex and PS NPs. Different pathways are used to enter the cells depending on the presence or absence of EGF. In the presence of EGF, cellular uptake of PS NPs is via clathrin-mediated endocytosis, whereas, in the absence of EGF, uptake of PS NPs does not involve clathrin-mediated endocytosis. Our findings indicate that EGF enhances cellular uptake of PS NPs by clathrin-mediated endocytosis. This result could be important for developing safe nanoparticles and their safe use in medical applications.

Highlights

Polystyrene nanoparticles (PS NPs) are widely used as a model for studying the interaction between NPs and cells due to their many advantages, including commercial availability, high quality, diverse sizes and shapes, biocompatibility, biological non-toxicity, and high functionality due to the presence of many chemical groups [1,2,3]
Our results indicate that epidermal growth factor (EGF) enhances the uptake efficiency of PS NPs by clathrin-mediated endocytosis, inducing the aggregation of EGF receptors on the cell membrane surface
The uptake ratio of PS NPs was signiffiicantly reduced in cells treated with sucrose and EGF, simiillaarr too thatt of cells not treated with EGF. These results showed that sucrose decreased the effect of EGF on cellular uptake of PS NPs

Summary

Introduction

Polystyrene nanoparticles (PS NPs) are widely used as a model for studying the interaction between NPs and cells due to their many advantages, including commercial availability, high quality, diverse sizes and shapes, biocompatibility, biological non-toxicity, and high functionality due to the presence of many chemical groups [1,2,3]. Most PS NPs are less than 100 nm in diameter and could potentially enter mammalian cells [2]. PS NPs have been reported to internalize in many types of cells, such as hepatocyte [8], macrophage [9], lung [10], and epithelium [11]. Previous studies showed that PS NPs can enter cells by several pathways, including phagocytosis, clathrin-coated vesicles, caveolae-mediated endocytosis, and macropinocytosis [12,13,14]. The internalization of NPs is affected by a variety of NP factors, such as target dose, particle size, cell type, NP morphology and surface chemistry, NP geometry, and by cellular responses, such as the cell cycle phase [15,16,17,18,19,20].

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