Assessment of Polyethylene Glycol-Coated Gold Nanoparticle Toxicity and Inflammation In Vivo Using NF-κB Reporter Mice

Abstract

Polyethylene glycol (PEG) coating of gold nanoparticles (AuNPs) improves AuNP distribution via blood circulation. The use of PEG-coated AuNPs was shown to result in acute injuries to the liver, kidney, and spleen, but long-term toxicity has not been well studied. In this study, we investigated reporter induction for up to 90 days in NF-κB transgenic reporter mice following intravenous injection of PEG-coated AuNPs. The results of different doses (1 and 4 μg AuNPs per gram of body weight), particle sizes (13 nm and 30 nm), and PEG surfaces (methoxyl- or carboxymethyl-PEG 5 kDa) were compared. The data showed up to 7-fold NF-κB reporter induction in mouse liver from 3 h to 7 d post PEG-AuNP injection compared to saline-injected control mice, and gradual reduction to a level similar to control by 90 days. Agglomerates of PEG-AuNPs were detected in liver Kupffer cells, but neither gross pathological abnormality in liver sections nor increased activity of liver enzymes were found at 90 days. Injection of PEG-AuNPs led to an increase in collagen in liver sections and elevated total serum cholesterol, although still within the normal range, suggesting that inflammation resulted in mild fibrosis and affected hepatic function. Administrating PEG-AuNPs inevitably results in nanoparticles entrapped in the liver; thus, further investigation is required to fully assess the long-term impacts by PEG-AuNPs on liver health.

Concomitant Sub-Chronic Administration of Small-Size Gold Nanoparticles Aggravates Doxorubicin-Induced Liver Oxidative and Inflammatory Damage, Hyperlipidemia, and Hepatic Steatosis

“…Short and long-term treatment with DOX was associated with higher levels of hepatic ROS, TNFα, and IL-6, over-activation of NF-κB, and reduced activities and expression of Nrf2 [ 3 , 4 , 6 , 8 , 30 , 31 , 32 ]. In addition, short-term treatment with AuNPs promotes hepatic and renal oxidative stress and inflammation by generating ROS and inflammatory cytokines, scavenging GSH, consuming SOD and CAT, and activating NF-κB [ 15 , 16 , 18 , 19 , 21 ]. Of note, the effect of AuNPs on hepatic and systemic Nrf2 signaling is not yet established in humans or animals.…”

“…However, the safety of these NPs is still uncertain. At the experimental levels, we and others have previously shown that short-term (7 days) exposure to small-sized gold NPs has resulted in a high rate of accumulation in the liver, and this was associated with high levels of ROS, lipid peroxidation, oxidative stress, activation of NF-κB, upregulation of inflammatory cytokines, and liver damage [ 15 , 16 , 17 , 18 , 19 , 20 ]. However, the effect of long-term exposure to AuNPs, as well as their combined effect with another risk factor on the liver structure and function is not well characterized.…”

PrPC Aptamer Conjugated–Gold Nanoparticles for Targeted Delivery of Doxorubicin to Colorectal Cancer Cells

“…In particular, it is known that the toxicity of AuNP can be significantly reduced through surface modification. In general, PEG is widely used to reduce the toxicity of AuNPs [ 22 , 68 ]. Patlolla et al showed that the PEG coating of AuNPs reduced the ROS generation and hepatotoxicity compared to uncoated AuNPs [ 69 ].…”

“…As AuNPs are known to be potentially toxic, several studies have been conducted to overcome this issue through surface modification. Various biological materials, including DNA [ 20 ], polyethylene glycol (PEG) [ 21 , 22 ], polyamidoamine [ 23 ], cell-penetrating peptides, and chitosan [ 24 , 25 ] have been used to enhance the biocompatibility of AuNPs. Furthermore, nucleic acid components can also be used to enhance drug loading.…”

Intracellular Exposure Dose-Associated Susceptibility of Steatotic Hepatocytes to Metallic Nanoparticles

“…Liver toxicity is a pivotal concern for risk assessment of environmentally exposed MNPs, as the liver is the major organ where MNPs are deposited and metabolized. In healthy adult rodents, MNP exposure caused hepatic inflammation, oxidative stress, DNA damage, and hepatocyte apoptosis and/or necrosis [ 34 , 35 , 36 ]. The above adverse outcomes in response to MNP exposure may be further aggravated in rodent models of NAFLD [ 13 ], suggesting the susceptibility of NAFLD individuals to MNPs.…”