Induction of oxidative stress and sensitization of cancer cells to paclitaxel by gold nanoparticles with different charge densities and hydrophobicities

Abstract

Gold nanoparticles with various positive charge densities and hydrophobicities induce cellular oxidative stress differently and sensitize cancer cells to paclitaxel.

Cytotoxicity-Related Bioeffects Induced by Nanoparticles: The Role of Surface Chemistry

“…A library of GNPs (6 nm) with continuously changing positive charge/negative charge density was constructed by varying the ratio of positively/negatively charged ligands to neutrally charged ligands. In HeLa, HEK293, and A549 cells, Su et al (2012)and Sun et al (2018) found that the level of GNP endocytosis was positively correlated with a positive charge density, while negative charge density had no significant influence on cellular uptake (Figure 2). Therefore, in multiple immune and non-immune cells, positively charged GNPs are more prone to endocytosis than are neutral and negatively charged GNPs.…”

“…In our previous study, cellular uptake level of hydrophobic and positively charged GNPs (6 nm) was positively correlated with oxidative stress level in A549 cells. Inhibition of GNPs' internalization led to the decrease of oxidative stress level, indicating that oxidative stress induced by GNPs is internalization-dependent (Sun et al, 2018). Therefore, for certain NPs, cellular uptake is positively correlated with cytotoxicity.…”

“…By varying the ratio of hydrophobic ligands to hydrophilic ligands on the NP surface, a GNP library (6 nm) with continuously changing hydrophobicity was synthesized. In HEK293, A549, and THP-1 cells, the cellular uptake levels were found to be positively correlated with the hydrophobicity of the GNPs (Figure 4) (Li et al, 2015a;Sun et al, 2018).…”

“…The cellular uptake of NPs is strongly associated with various cytotoxicity-related bioeffects, including oxidative stress, apoptosis, autophagy, and inflammation (Xia et al, 2008;Foldbjerg et al, 2011;Stern et al, 2012;Sun et al, 2018). For example, Xia et al found that ZnO NPs (13 nm) internalized by RAW264.7 cells elicited oxidative stress, inflammation, and cell death (Xia et al, 2008).…”

“…After exposing GNPs to A549 and HEK293 cells, we found that positive charge density was positively correlated with ROS level, while negative charge density exhibited no impact on intracellular ROS level. Studies on ROS-related mechanisms indicated that the cellular uptake of positively charged GNPs induced cell membrane depolarization and calcium channel opening and ultimately stimulated mitochondria to generate intracellular oxidative stress (Figure 5A) (Sun et al, 2018). In another study, it was also found that positively charged PEI-GNRs (55.7 × 13.2 nm) led to a decrease in intracellular GSH levels and GSH/GSSG ratios in A549 cells, while negatively charged PSS-GNRs exhibited no influence on GSH levels .…”