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Surface Charge-Dependent Cellular Uptake of Polystyrene Nanoparticles.

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.

SUBMITTER: Jeon S

PROVIDER: S-EPMC6316338 | biostudies-literature | 2018 Dec

REPOSITORIES: biostudies-literature

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Project description:BackgroundPolymer nanoparticles (PNP) are becoming increasingly important in nanomedicine and food-based applications. Size and surface characteristics are often considered to be important factors in the cellular interactions of these PNP, although systematic investigations on the role of surface properties on cellular interactions and toxicity of PNP are scarce.ResultsFluorescent, monodisperse tri-block copolymer nanoparticles with different sizes (45 and 90 nm) and surface charges (positive and negative) were synthesized, characterized and studied for uptake and cytotoxicity in NR8383 and Caco-2 cells. All types of PNP were taken up by the cells. The positive smaller PNP45 (45 nm) showed a higher cytotoxicity compared to the positive bigger PNP(90) (90 nm) particles including reduction in mitochondrial membrane potential (ΔΨ(m)), induction of reactive oxygen species (ROS) production, ATP depletion and TNF-α release. The negative PNP did not show any cytotoxic effect. Reduction in mitochondrial membrane potential (ΔΨ(m)), uncoupling of the electron transfer chain in mitochondria and the resulting ATP depletion, induction of ROS and oxidative stress may all play a role in the possible mode of action for the cytotoxicity of these PNP. The role of receptor-mediated endocytosis in the intracellular uptake of different PNP was studied by confocal laser scanning microscopy (CLSM). Involvement of size and charge in the cellular uptake of PNP by clathrin (for positive PNP), caveolin (for negative PNP) and mannose receptors (for hydroxylated PNP) were found with smaller PNP45 showing stronger interactions with the receptors than bigger PNP(90).ConclusionsThe size and surface characteristics of polymer nanoparticles (PNP; 45 and 90 nm with different surface charges) play a crucial role in cellular uptake. Specific interactions with cell membrane-bound receptors (clathrin, caveolin and mannose) leading to cellular internalization were observed to depend on size and surface properties of the different PNP. These properties of the nanoparticles also dominate their cytotoxicity, which was analyzed for many factors. The effective reduction in the mitochondrial membrane potential (ΔΨ(m)), uncoupling of the electron transfer chain in mitochondria and resulting ATP depletion, induction of ROS and oxidative stress likely all play a role in the mechanisms behind the cytotoxicity of these PNP.

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Surface Charge-Dependent Cellular Uptake of Polystyrene Nanoparticles.

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