The Effects of Polymer Coating of Gold Nanoparticles on Oxidative Stress and DNA Damage

Abstract

Gold nanoparticles (AuNPs) have been widely used in many biological and biomedical applications. In this regard, their surface modification is of paramount importance in order to increase their cellular uptake, delivery capability, and optimize their distribution inside the body. The aim of this study was to examine the effects of AuNPs on cytotoxicity, oxidant/antioxidant parameters, and DNA damage in HepG2 cells and investigate the potential toxic effects of different surface modifications such as polyethylene glycol (PEG) and polyethyleneimine (PEI; molecular weights of 2,000 (low molecular weight [LMW]) and 25,000 (high molecular weight [HMW]). The study groups were determined as AuNPs, PEG-coated AuNPs (AuNPs/PEG), low-molecular weight polyethyleneimine-coated gold nanoparticles (AuNPs/PEI LMW), and high-molecular weight polyethyleneimine-coated gold nanoparticles (AuNPs/PEI HMW). After incubating HepG2 cells with different concentrations of nanoparticles for 24 hours, half maximal inhibitory concentrations (the concentration that kills 50% of the cells) were determined as 166.77, 257.73, and 198.44 µg/mL for AuNPs, AuNPs/PEG, and AuNPs/PEI LMW groups, respectively. Later, inhibitory concentration 30 (IC30, the concentration that kills 30% of the cells) doses were calculated, and further experiments were performed on cells that were exposed to IC30 doses. Although intracellular reactive oxygen species levels significantly increased in all nanoparticles, AuNPs as well as AuNPs/PEG did not cause any changes in oxidant/antioxidant parameters. However, AuNPs/PEI HMW particularly induced oxidative stress as evidence of alterations in lipid peroxidation and protein oxidation. These results suggest that at IC30 doses, AuNPs do not affect oxidative stress and DNA damage significantly. Polyethylene glycol coating does not have an impact on toxicity, however PEI coating (particularly HMW) can induce oxidative stress.

Neuroprotective Effect of Gold Nanoparticles and Alpha-Lipoic Acid Mixture against Radiation-Induced Brain Damage in Rats

“…Herein, treatment of irradiated rats with AuNPs led to a dose-dependent elevation in the DNA content in cortical and hippocampal tissues. Noteworthy, there are competing findings in the literature concerning the effect of AuNPs on DNA damage [ 60 ], which may be attributed to the particle size of AuNPs [ 58 ]. Ultra-small particles can perfectly fit into the major grooves of the DNA, thereby immobilizing it [ 61 , 62 ].…”

Assessment of the Potential Health Risk of Gold Nanoparticles Used in Nanomedicine

“…But unlike us, they determined the depletion of SOD and catalase activities in mentioned cancer cell line. Oxidative Medicine and Cellular Longevity Sen et al [9] also studied the effects of Au NPs (size of 55-65 nm, concentrations 25-400 μg/mL, and 24 h incubation) on the oxidative stress of HepG2 cells characterized by activities of GPx, SOD, and catalase, as well as on the lipid peroxidation and protein oxidation. Compared to the control, they found no effects either on enzymatic activities or protein carbonyl level and lipid peroxidation characterized by malondialdehyde level.…”

“…Metal NPs, especially noble metal NPs, form a special group of NPs with an application in medicine. The surface of these materials can be modified in many ways with several chemical functional groups which enable them to conjugate with for example ligands, antibodies, or drugs [8,9]. Depending on the treatment of NPs surface, their properties also unfold.…”

Green synthesis of gold nanoparticles for immune response regulation: Mechanisms, applications, and perspectives

“…A common approach to address this potential toxicity is overcoating GNPs with polymers 49,50 . However, their use is limited by poor reproducibility and stability of the system and potential toxicity generated by the polymer coating, causing oxidative stress and DNA damage 51,52 …”