Molecular origin of AuNPs-induced cytotoxicity and mechanistic study

Abstract

Gold nanoparticles (AuNPs) with diverse physicochemical properties are reported to affect biological systems differently, but the relationship between the physicochemical properties of AuNPs and their biological effects is not clearly understood. Here, we aimed to elucidate the molecular origins of AuNP-induced cytotoxicity and their mechanisms, focusing on the surface charge and structural properties of modified AuNPs. We prepared a library of well-tailored AuNPs exhibiting various functional groups and surface charges. Through this work, we revealed that the direction or the magnitude of surface charge is not an exclusive factor that determines the cytotoxicity of AuNPs. We, instead, suggested that toxic AuNPs share a common structural characteristics of a hydrophobic moiety neighbouring the positive charge, which can induce lytic interaction with plasma membrane. Mechanistic study showed that the toxic AuNPs interfered with the formation of cytoskeletal structure to slow cell migration, inhibited DNA replication and caused DNA damage via oxidative stress to hinder cell proliferation. Gene expression analysis showed that the toxic AuNPs down-regulated genes associated with cell cycle processes. We discovered structural characteristics that define the cytotoxic AuNPs and suggested the mechanisms of their cytotoxicity. These findings will help us to understand and to predict the biological effects of modified AuNPs based on their physicochemical properties.

The Rational Design and Biological Mechanisms of Nanoradiosensitizers

“…The surface charge of NPs can regulate the oxidative stress level in cancer cells. We and other researchers have found that the intracellular ROS level is positively correlated with positively charged NPs, such as GNPs [68][69][70], polyethylenimine (PEI)-decorated GNRs [71], single-walled carbon nanotubes (SWCNTs) [72], ZnO NPs (98 nm, 11.1 mV) [73], upconversion (UCNP)@SiO 2 NPs with NH 2 decoration (37 nm, 26.2 mV) [74], and glucose-decorated iron oxide NPs (70 nm) [75]. In addition, we found that, in A549 cells, hydrophobic GNPs are more likely to induce oxidative stress than are hydrophilic NPs [68].…”

Chitosan-Coated Gold Nanoparticles Induce Low Cytotoxicity and Low ROS Production in Primary Leucocytes, Independent of Their Proliferative Status

“…CH-AuNPs and SC-AuNPs showed similar polydispersity (0.3 for both); however, CH-AuNPs had a positive charge (+36.7 mV) compared to a negative charge for SC-AuNPs (−10 mV). Other cationic AuNPs showed similar cytotoxicity in a cervical cancer cell line (HeLa) and in a normal human dermal fibroblast cell line (NHDF) [27]. Physicochemical properties such as surface, size, and dispersity of NPs also determine their biological impact.…”

“…The dispersity of NPs is involved in cytotoxicity, and may be related to the increase of cellular endocytosis and ROS [26]. Additionally, the interaction between cationic AuNPs and negatively charged plasma membrane were shown to be determinant for the cytotoxicity [27,28], and this positive charge of the CH-AuNPs could be also determine the selectivity to cancer cells. CH-AuNPs and SC-AuNPs showed similar polydispersity (0.3 for both); however, CH-AuNPs had a positive charge (+36.7 mV) compared to a negative charge for SC-AuNPs (−10 mV).…”

Advances and potential application of gold nanoparticles in nanomedicine

“…Recently, a study showed that cytotoxicity of AuNPs is dependent on surface charge and their capacity to induce lytic interaction with the plasma membrane. Also, AuNPs interfere with cell migration, inhibit DNA replication, and promote DNA damage . Altogether these data show that more studies are necessary to better understand the cytotoxicity potential of AuNP, contributing to safe use of these NPs in nanomedicine.…”