Abstract

The evaluation of the role of physicochemical properties in the toxicity of nanoparticles is important for the understanding of toxicity mechanisms and for controlling the behavior of nanoparticles. The surface charge of nanoparticles is suggested as one of the key parameters which decide their biological impact. In this study, we synthesized fluorophore-conjugated polystyrene nanoparticles (F-PLNPs), with seven different types of surface functional groups that were all based on an identical core, to evaluate the role of surface charge in the cellular uptake of nanoparticles. Phagocytic differentiated THP-1 cells or non-phagocytic A549 cells were incubated with F-PLNP for 4 h, and their cellular uptake was quantified by fluorescence intensity and confocal microscopy. The amount of internalized F-PLNPs showed a good positive correlation with the zeta potential of F-PLNPs in both cell lines (Pearson’s r = 0.7021 and 0.7852 for zeta potential vs. cellular uptake in THP-1 cells and nonphagocytic A549 cells, respectively). This result implies that surface charge is the major parameter determining cellular uptake efficiency, although other factors such as aggregation/agglomeration, protein corona formation, and compositional elements can also influence the cellular uptake partly or indirectly.

Highlights

  • Nanomaterials are applied as various biomedical tools including diagnostic, monitoring, and therapeutic tools [1,2,3,4,5]

  • The surface charge of PLNPs was measured using a Malvern Zetasizer Nano-ZS in distilled water (DW), and in actual media where PLNPs were in contact with phenol red-free Roswell Park Memorial Institute-1640 (RPMI-1640; Corning, Corning, NY, USA) for THP-1 cells and phenol red-free Dulbecco’s modified Eagle medium (DMEM; Corning) for A549 cells

  • The zeta potential of nanoparticles ranged from −41 to +42 mV in DW, while the zeta potential of nanoparticles in culture media showed negative charges for all nanoparticles without overlapping between nanoparticles: −42 to −27 mV in phenol red-free RPMI-1640 and −47 to −32 mV in phenol red-free DMEM

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Summary

Introduction

Nanomaterials are applied as various biomedical tools including diagnostic, monitoring, and therapeutic tools [1,2,3,4,5]. The surface modification of nanomaterials, which is essential for these applications to improve their physicochemical properties, can affect the biocompatibility of the materials by changing their inflammogenic potential [6,7], cytotoxicity [8], or toxicokinetics [9]. Surface charge is suggested as one of the major factors which control various biological responses to nanomaterials. Positively charged polyethylene glycol/polymeric nanoparticles showed a favorable distribution and higher bioavailability in Caco-2 cells and in vivo models compared to negatively charged particles [12]. Charged particles were shown to have a higher uptake efficiency than negatively charged particles; there are still discrepancies between studies and further studies using well-engineered nanoparticles, and relevant cell types are needed

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